The following is a conversation between Professor Scott O’Neill, Director of the World Mosquito Program, and Denver Frederick, the Host of The Business of Giving.

Professor Scott O’Neill, Director of the World Mosquito Program

Denver: And it’s a pleasure to welcome to the show one of the six finalists of the MacArthur Foundation’s 100&Change competition. He is Scott O’Neill, the Director of the World Mosquito Program.

Welcome to The Business of Giving, Scott, and congratulations on being named one of the superlative six!

Scott: Thanks, Denver. It’s good to be here.

Denver: Tell us what the mission of the World Mosquito Program is.

Scott: So, we are really focused on a collection of diseases that are transmitted between people in the tropics by one mosquito, and we found a novel way of stopping the mosquito from transmitting those diseases. Our goal over the next five years is to be able to protect around 75 million to 100 million people from catching diseases from the mosquitoes.

Denver: That’s quite ambitious. Well, one of those diseases is dengue. I think it’s the world’s fastest-growing tropical disease. What is it, and how many people are infected by it?

Scott: So dengue is a collection of viruses that infect people and can make them very, very sick. It’s estimated that around 400 million people globally get infected each year, and potentially 40% of the global human population is at risk of getting one of these diseases each year. So it’s a big, big problem. There’s no current solution, and it’s getting worse. And so if you live in a tropical city anywhere in the world, you would know about diseases like dengue because you’re constantly at risk of getting them.

Denver: You know, if I were to get dengue, as an example, what would happen? What’s the impact of it on me?

Scott: So, there’s a spectrum of disease that people experience. Some people have fairly mild symptoms, and some people are completely asymptomatic, don’t get sick at all, but what typically happens is you develop a rash on your body, have very high fever, severe pain behind your eyes, metallic tastes in your mouth. If it starts getting bad, you start internal bleeding, go into shock and die. And it’s so prevalent and it’s so common that typically we see the disease in children in tropical regions of the world, in the big cities of the world where this mosquito likes to live.

Denver: You said “this mosquito.” What kind of mosquito are we talking about?

Scott: It’s called Aegis Aegypti. It’s a very famous mosquito. It’s a little black and white guy who likes to live right as close as it can to people. It likes to bite people to get blood, and that blood it uses to grow, to mature its eggs, to lay eggs. And because it likes people so much, it likes to live with them, lives inside the houses with them, and typically bites people inside. And because it’s biting people all the time, it’s a very good vector to transmit a range of viruses that create sickness like dengue, yellow fever, chikungunya, zika, the list goes on and on. And so it’s a major, major pest of humans.

Denver: Wow. Well, your intervention innovation is to disrupt that transmission with a natural bacteria called Wolbachia. How does that work? What is it?

Scott: Yes. So, Wolbachia is a fairly obscure bacterium. So we’ve known about it since the 1920s, but it’s only in very recent years that people have spent a lot of time working on it. And what we found is that this bacteria occurs naturally in about half of all the insect species on the planet, but it doesn’t occur in this mosquito that transmits all these diseases.

And what we found is when you put the bacteria called Wolbachia into the mosquitoes, the mosquitoes can no longer support the growth of these viruses that I’ve just mentioned. And without growing in the mosquito, it can’t be transmitted between people. So, very simple intervention. We put the bacteria into the mosquito, and the really cool part about this is that the bacteria gets transmitted from one generation to the next in the mosquito–

Denver: that’s incredible.

Scott: –and maintains itself. Yes. So, it maintains itself in the population and then shuts down the ability of the mosquito to transmit these viruses to people.

Denver: I’m trying to picture this a little bit because you say when we apply or inject this bacteria into the mosquito… spell that out a little bit. How in the world do you do that?

Scott: Yes, so, sometimes this creates a bit of confusion with people. We don’t have to do it every time. We just have to do it once, and the reason is because once the mosquito has this Wolbachia bacteria, it passes it down itself to its children through its eggs, through the mosquitoes’ eggs, but we had to spend a lot of time to get that first female mosquito infected with Wolbachia so then we could generate a colony of mosquitoes that contain it, and that required very painstaking work for many, many years to be successful.

Denver: And then I guess what you do is you release these mosquitoes into the community? Tell us a little bit about how that works and how you get the community to embrace what you are doing?

Scott: So, when we were able to establish these mosquito lines in our laboratory that contain Wolbachia, we just have to breed them then. And then the idea is that we release them into the community and they bring the Wolbachia with them, and then the Wolbachia spreads into the local mosquito population and stays potentially indefinitely, and so it gives ongoing protection then.

So the key thing then is that we have to release mosquitoes into a community, and these are the mosquitoes that will bite people. And so, you could imagine that communities would be concerned about an intervention like this. You could imagine if people were coming around releasing mosquitoes around your house that are going to bite you. Because of this, we take community engagement very, very seriously, and we spend a lot of time talking to communities, explaining what we’re doing, answering their questions.

And what we find is the community in every location we’ve worked has become incredibly supportive and actually get involved in releasing the mosquitoes themselves. And so, why? Why would they do that? And the reason is that people are very fearful of dengue and diseases like dengue, and nothing’s working. Nothing is controlling these diseases at the moment and people are desperate for a solution. And so, when they understand what we’re doing, they understand it’s safe, and that it can have an impact, then we find that they become huge supporters of the work we are doing.

Denver: Yes, I can imagine. There’s got to be different strategies for different communities because they all have their own particular things that you really have to customize the pitch.

Scott: Yes. Obviously. And really that’s about the key element here is about the trust. And it’s about us being authentic with the people we work with, explaining what we know, what we don’t know, what the risks are, et cetera. and letting the community have a decision, an authentic decision in whether this is something they want or don’t want. And when we approached it that way, we’ve not found a community that didn’t want it. Sometimes, they may be resistant initially, but once they learn about it, once they see what the effect it’s having in neighboring areas and how positive it is, we find that they become huge supporters.

Denver: Good stuff. Well, let’s talk about a couple of those communities. And let me start with one of the first, which would be North Queensland in Australia. Tell us about what happened there and the impact that this has had now that you’ve done it.

Scott: Yes. So in Northern Australia, in the regional towns and cities of Northern Australia, dengue has been a problem for around a hundred years or more. It’s not what we call endemic transmission, so it doesn’t persist there, but it gets introduced every year in travelers bringing the virus in, and then the mosquitoes are there and they spread it. So, we developed all of this work in Australia and we felt that we wanted to test it out in our own backyard before testing it in communities in the developing world.

And so, North Queensland was the place we went, and we spent a lot of time talking to the community there. They ended up being extremely supportive of what we’re doing, not just for their own health but in a very altruistic way for the health of people in neighboring countries as well. They wanted to do something supportive of our neighbors in Indonesia and in other areas. And we ended up releasing the mosquitoes there 10 years ago now it was, and we release mosquitoes for 10 weeks. The Wolbachia is maintaining itself still after that 10 weeks released now 10 years later, and dengue transmission has collapsed now in Australia. We haven’t seen any serious dengue outbreaks since the mosquitoes were released. So it’s been—

Denver: That’s fantastic.

Scott: — quite a dramatic effect we’ve seen in North Queensland. And then you don’t need to be a scientist or a mathematician or something to do the statistics to work out how effective this was. It’s very visible and very visible to the people that live in the communities that there’s no dengue there anymore.

Denver: And one of your more recent studies was from Indonesia. Tell us about that.

Scott: Yes. So in the last 10 years or so, we’ve been accumulating evidence of impact. And there are different ways that you can determine how big the impact is you are having, and the gold standard is called a randomized control trial. It’s large, it’s expensive. It’s challenging to do. And we went to the city of Yogyakarta in Central Java in Indonesia, and we set up 24 clusters of which half got the Wolbachia and half didn’t across the city of around 300,000 people. And then we measured the dengue in those clusters, let’s say more or less in areas that got Wolbachia and areas that didn’t. And what we measured was that in areas that got Wolbachia, we measured a 77% reduction in virologically confirmed dengue — that’s lab-confirmed dengue — which some people would say, “Well, what does that mean, 77%?” And I can say 77% in this sort of clinical trial is a very, very big number for a disease reduction.

And our expectation is that if we were to now, which we’re doing, fill in the rest of the city with Wolbachia, we would be measuring a bigger impact than 77% and potentially complete elimination in the city. And what’s different about this city from Australia is this: we’re talking about a very intense transmission setting here in Indonesia where most children will get dengue by the time they’re seven and have had it once at least.

…this mosquito transmits a range of viruses, not just dengue: Zika, chikungunya, yellow fever. The list is a very long list. And what we’ve found is that when the Wolbachia is in the mosquito, it doesn’t just block dengue. It blocks all of these viruses.

Denver: You touched on this a moment ago but we’re talking about dengue. But what are some of the other diseases where this Wolbachia is being used with these mosquitoes and are also seeing a reduction?

Scott: Yes. So really, one of the most amazing things about what we’re doing, I think, is that this mosquito transmits a range of viruses, just dengue, Zika, chikungunya, yellow fever. The list is a very long list. And what we’ve found is that when the Wolbachia is in the mosquito, it doesn’t just block dengue. It blocks all of these viruses. And so, it’s one intervention that can potentially target five or six different diseases simultaneously.

But it becomes a little bit more difficult to measure the impact on some of these other diseases because they’re more sporadic. They’re not always present in the community year after year, and so you have to be doing a trial in the right place at the right time to be able to capture them. But we have done that in Brazil. We’re seeing significant reduction similar to what we see with dengue. We’re measuring it with chikungunya at the moment and Zika, which was just a terrible, terrible thing a few years ago through the Americas. It sort of disappeared for the moment, and we’re waiting for it to reappear, which everybody is expecting to happen in the next couple of years, and then we’ll be able to get the direct measurement on Zika as well. But all of the data at the moment suggests major impact on all of these diseases simultaneously.

Denver: Scott, what has been the impact of the coronavirus on your work, your ability to make progress, and maybe even the return of dengue in some places where you haven’t been able to continue that work?

Scott: Well that’s interesting because people like myself spend a lot of time on planes, flying around, and so there’s been an immediate impact that we were all grounded, and we haven’t been able to fly. Actually, a lot of us got stranded in countries where we live, including myself. I got stranded for eight months out of Vietnam where I live. But more broadly, because we’re seeing communities locked down, a lot less movement of people going on, people are in their houses more. That’s exactly where you get dengue, in your house. That’s where the mosquitoes like to live.

And so, on top of that, the current methods of control which often rely on insecticide use or spraying and fogging insecticides to try and kill the mosquitoes, a lot of that’s not happening because everybody, all the government resources, particularly in developing countries, are like 100% focused on COVID at the moment. And so what we’re seeing in some places is dengue is roaring along in the background quietly, and nobody is really measuring it or watching it at the moment. But the problem has gotten worse while we’ve been under COVID.

Dengue puts a large economic burden on communities where it affects people, and the biggest problem associated with dengue is the social and economic costs of the disease rather than the direct mortality.

Denver: Scott, is there an economic case to be made for this program, and along the same lines, what are you doing to try to reduce your costs in administering it?

Scott: So, dengue puts a large economic burden on communities where it affects people, and it’s really the biggest problem associated with dengue is the social and economic costs of the disease rather than the direct mortality. It knocks people out of earning a living; it increases poverty; it puts stress on the healthcare system, et cetera.

Our current cost of deploying the intervention is somewhere between $5 to $10 per person. At that level in urban settings, it’s predicted to be cost saving for governments. In other words, governments spend more than that in trying to control dengue and in direct medical costs associated with it. So currently, we’re looking to be cost-saving, which is fantastic for an intervention like this. We would like it to be even more compelling by reducing the cost to below a dollar per person protected if possible, and we were wanting to achieve that through economies that we have achieved through scaling. And so to be able to work it a bigger scale, and as a result lower our costs.

Denver: Talk about that scaling a little bit. How many people have you been able to reach so far and that objective that you’re shooting for?

Scott: Currently, we’re working with projects in 12 countries, and we have protected around 5.3 million people already in the work we’ve been doing, which has really been research-focused if you look at the work we’ve done so far. We’re pivoting now to really talk about scale-up, and our goal over the next five years…our initial goal was to reach a hundred million people. We’ve downsized that prediction a little bit, that goal a little bit, due to COVID. And we feel like 75 million is the goal that’s more achievable for us, and that’s what we’re going to be targeting for the next five years… to protect 75 million people across a range of countries.

Denver: You know, a big plus of that goal would be the endorsement of the World Health Organization. That would be so helpful. Where do you stand with that?

Scott: The World Health Organization rightly so wants to see the evidence of impact, and the gold standard evidence is the big trial that we’ve just run and completed in Indonesia. We have a big package of our evidence going up to the World Health Organization at the end of this year for review, and we’re hoping that we will receive endorsement by then from the World Health Organization to take our method forward.

Denver: As one of the six finalists of the 100&Change competition, I’d like to ask you a little bit about problem-solving, because here you are on the front end of one of the best solutions, but I know you just don’t waltz into that solution. There’s a lot of thinking that goes on, a lot of defining of the problem, reframing the problem, disaggregating the problem… just tell us a little bit of the process that got you from looking at this challenge and how this intervention came to pass?

Scott: We’ve been working on this for years and years and years. It feels like my entire professional life has been spent on this. And I have to say, many times along that path, the progress has been very slow to non-existent. And so, I often get asked the question about the journey that we’ve been on in developing this. And the thing that sticks in my mind is that I think it requires a little bit of obsessive personality disorder that you’re willing to just keep going at it because you think the idea is good and you want to succeed with it, and you think it should work.

And so we’ve gone for periods of years without a positive result, and we keep trying and trying. And I sort of think… I’ve been thinking about it a bit: I don’t think that many people have that many good ideas in their life. Even the most brilliant people out there, they only have a couple of really good ideas, and we’ve always felt this is a good idea.

Denver: Yes. I sort of see that when I look at somebody who writes a great book, and they might write five other books, but it’s the same book as the first book they wrote. They had one good idea for a book.

Scott: Yes. I think that’s pretty typical. And so because of that, and just the nature of doing science and you get used to failing a lot. We spent a lot of time failing. But then a few years ago, it all just started clicking in an amazing way. I almost felt like it was fated in some way, but it all started slotting into place. And after years and years of failure, we started getting positive results. And now it’s just so great to see the impact we’re starting to see it in communities after doing this work for 20 years or so, and it’s delightful!

…you get used to failing a lot. We spent a lot of time failing. But then a few years ago, it all just started clicking in an amazing way. I almost felt like it was fated in some way, but it all started slotting into place and after years and years of failure, we started getting positive results. And now it’s just so great to see the impact. We’re starting to see it in communities after doing this work for 20 years…

Denver: So, if you should be so fortunate to be declared the winner and win the $100 million award from the MacArthur Foundation, what would it allow you to do? How would you spend that money?

Scott: For us, it would be the facilitator of shifting and moving, transitioning if you like, from showing evidence, showing impact, showing that this is something with huge potential, to then transitioning into making that happen at scale. And so, it would be the catalyst that would allow us to move towards some of the requirements that would be needed: industrial scale production of mosquitoes, for example, to be able to get them out to communities at scale, to form the partnerships with trusted groups on the ground that allow us to implement it across the entire cities and multiple cities, and to reach our target of 75 million to 100 million people over the next five years.

So, it would be an incredible opportunity for us if we were to receive that amount of money. And I think it would completely de-risk, if you like, this intervention by showing that we can get it to that scaling to then keep it moving after this. It needs to reach the 40% of the world’s population that’s at risk. And so this would be a critical injection of confidence of funding to be able to get us on that path, to have really major global impact.

Denver: Let me close with this, Scott. You clearly have some very formidable and worthy competition in the other finalists, and I am in no way trying to compare your project to theirs, but what case would you make as to why the World Mosquito Program would make a very deserving winner?

Scott: Well, firstly I’d like to say that I’ve had a brief look at the other finalists and I think all of their work, it’s just fantastic. And so, I think the board has a very difficult decision to make. I think all of the projects are really worthy.

In our case, we’re looking at a global disease, a set of diseases actually, for which there’s no solution at the moment and hasn’t ever been a solution. And these are diseases that help entrench poverty, that prevent development, that have devastating effects on people’s individual lives. And you don’t have to spend very long looking at this terrible situation: Zika babies being born with major developmental defects, putting very poor families into situations where they need to care for a very disabled child in an environment where there’s no safety net for those people.

And what we have found and been so lucky to work on is a situation where we can stop that, and we can prevent a whole range of diseases and people getting sick from them. And so, I think it’s a very unusual situation we found ourselves in to have been able to find the solution. And just because of the enormity of the problem and the lack of any solutions at the moment, I think it makes a very worthy case for investment. So, we’re hopeful that MacArthur or some other group, if not MacArthur, might feel that’s the case as well.

Denver: You made a very worthy case just there. This is such interesting work. Where can listeners find out more about it?

Scott: We have a very comprehensive website that tells people very much about what we’re doing, where we’re working, the background story to what we do. It’s

Denver: Well, best of luck to you and to your team, Scott, and the MacArthur Foundation’s 100&Change competition. It was a real delight to have you on the program.

Scott: Thanks, Denver. Thank you.

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