Gene Drive Technology: A Hopeful Solution for Malaria

Abdoulaye Diabaté believes gene drive technology can eliminate malaria in Africa, transforming lives and offering hope for a healthier future.

### Fighting Malaria: Innovative Approaches and Community Engagement
* 🦟  Mosquitoes have long been a nuisance, and they are also the primary vectors for malaria, a disease that has plagued humanity for centuries, particularly affecting **millions in Africa and Asia today**.
* 🌍  Despite successful malaria control in the US and Europe, there are still approximately **200 million cases globally each year**, resulting in around **600,000 deaths**, with **children and pregnant women being the most vulnerable**.
* 💔  Abdoulaye Diabaté, a medical entomologist, shares his personal experience as a childhood malaria survivor and emphasizes the **ongoing struggle against this disease**, highlighting the **complex interplay between the pathogen, vector, and human host**.
* 🧬  Diabaté introduces the concept of gene drive technology, which aims to control mosquito populations by altering their reproductive capabilities, potentially **stopping malaria transmission within just 20 generations, or roughly two years**.
* ⚠️  However, the implementation of gene drive technology faces challenges, including the need for **community acceptance**, **environmental concerns**, and the necessity of **building local scientific capacity** to ensure sustainable management of the technology.
* 🤝  Target Malaria is committed to engaging communities in the process, ensuring **transparency and inclusivity**, and developing a strategy that involves **local stakeholders from the outset**.
* 🏫  To address the knowledge gap, initiatives like the World Bank-funded center of excellence on vector-borne diseases are being established in Burkina Faso to **train the next generation of scientists**, empowering Africans to **lead the fight against malaria**.
* 🌟  Diabaté concludes with a vision of a **malaria-free world**, asserting, "**Yes, we can**," and emphasizing the importance of **hope and opportunity for every child**, regardless of their birthplace.

(Mosquitoes buzzing) Mosquitoes. I don't know about you, but I don't have a good relationship with them. (Laughter) A friend of mine said one day, If you think that you are too small to make a big difference, you've never spent a night with mosquitoes in a room. (Laughter) But ... I don't have any mosquitoes in my pocket to release tonight, so it's going to be fine. So let's start. As unbelievable as it may sound, malaria is as old as humankind. And malaria once was a public health issue all over the world. But then it has been successfully tackled in the US and Europe. And yet, decades later, malaria still kills millions of people in Africa and in Asia. Why? I'm Abdoulaye Diabaté, a medical entomologist from l'Institut de Recherche en Science de la Santé.

I'm here today, flying all the way from Burkina Faso, to tell you that we might be closer than ever to eliminate malaria in Africa. (Applause) Thank you. Malaria is tightly linked to poverty. But then you have no idea of how expensive it is to be poor. There are 200 million cases worldwide that end up sadly every year with about 600,000 deaths. And this is not a random collection of statistics on a piece of paper. Behind each of these 600,000 deaths, there is a personal, tragic story, sometimes behind closed doors. Most of these deaths happen in Africa. Children and pregnant women bear the highest burden. And I'm a fortunate childhood malaria survivor. When I was a kid, I used to think that my dad was a superhero. I could see him leaving the house every morning at six, riding his bicycle to the farm, working very hard all day long.

We did not have much for living. But who said you need more to be happy? But when happiness hangs by a thread, it doesn't take much to turn your life around. My certainty in my dad got deeply shaken the day I got struck down by malaria. I was three or four years old. As we used to say in my country, kids may not understand the complexity of suffering, but pain has no age. And gosh, I was in pain. I can still clearly see myself laying down there on the bed with high fever and suffering. I could not eat anything. Throwing up all the time. Will I survive? Will I not? The psychological trauma my parents were going through was unbearable. But against all odds, I survived. But can we say today that we are done with malaria because Diabaté survived and made it all the way down to Vancouver? If I say yes, no one can blame me. But it’s a lie, because many children are still dying of malaria.

The real question then is: Why have we not been able to defeat it so far? Well, because malaria is a complex parasitic disease that plays on three grounds: Plasmodium, the pathogen; anopheles, the vector; and human, the victim. Each of these elements is very complex on its own, and the interactions make it even more complex to devise interventions that are really effective. But of course, we are trying. Currently, there are two vaccines to immunize people, but the heavy logistics to deliver this vaccine may not allow us to reach their full potential. Bed nets and first-hand treatment are both threatened by insecticide and drug resistance, meaning that our best interventions have started to fail. And there is a general consensus today that without additional new tools, we may never cross the last mile of malaria elimination. And this is exactly where I come in. My colleagues and I at Target Malaria are working on something called gene drive:

a way to control mosquito population and halt malaria transmission. So what is gene drive? It's a natural molecular mechanism that augments the frequency of a certain gene in the population beyond the normal Mendelian inheritance. So what does it mean? If you take any gene, in natural circumstances, it has only a 50 percent chance of being transmitted to the next generation. Meaning that if the parents have 100 babies, like in mosquitoes, only 50 of them will get the gene and the other 50 will not. But not all genes behave this way in nature. Some genes have found a very clever way to bypass this law and can augment their own prospect to up to 90 percent. Such genes are said to drive, and so the name gene drive. Our most promising strain affects female fertility by targeting a gene called doublesex. This gene is responsible for the sex determination in mosquitoes, and so disrupting the doublesex gene

may affect the sexual development for adult mosquitoes and their reproduction. Now it may sound counterintuitive to affect female fertility and spread a gene of interest in the mosquito population at the same time. But it's working. And let me show you how. We target a specific region of the gene called doublesex that affects only females. Males bearing this modified gene are not affected at all. Females with just one copy of the altered gene are fully fertile. However, females bearing two copies of the modified gene cannot lay eggs, fail to bite, and also have the physical characteristics of both male and female. It's called a suppression strategy. Once these mosquitoes are released in the field, they're going to spread the gene of interest to the wild population, and this is going to reduce dramatically their reproductive capacity. Fewer mosquitoes mean less malaria transmission until it stops. Mathematical models predict that releasing such mosquitoes in the field is going to stop malaria transmission in just 20 generations.

That means in two years. And the technology is sustainable, cost-effective, and easy to deploy, as the released mosquitoes will do the job themselves by finding the last hiding pocket of wild mosquitoes to convert. Fantastic. The only problem, gene drive has never been tested anywhere in Africa. And while the technology brings a lot of hope, it also carries its share of fear and skepticism. The pathway from the bench to the field is not straightforward and is full of pitfalls. Maybe the mosquitoes in the field will develop resistance to the spread of the transgene. Or maybe two countries don't agree, but released mosquitoes do not respect the human borders. Or also, maybe there are risks to the environment. And finally, the community that we are working with needs to feel comfortable about this technology and give us the green light to operate. And so for such, Target Malaria has adopted an incremental approach, step by step, whereby we will start releasing first non-gene-drive mosquitoes,

meaning that the gene of interest here cannot self-propagate and will just go extinct in a few generations. The gene drive, the exposure of this gene to the environment is incrementally augmented in a way that we start first with small cages and big indoor cages in Europe, and then these mosquitoes are sent to Burkina Faso, where they are tested in a contained facility first, and subsequently in a big indoor small cage field release. Now the gene drive mosquitoes are going to be tested in an open field only after this preliminary step and the potential risks have been looked at very carefully. And also additional research questions have been developed to address these risks, if any. Now the question, how far are we from releasing gene drive? Four to five years. But let me tell you this. Gene drive mosquitoes are already in the lab, and releasing them in the field is not going to take us more than 30 minutes. But we need five years to get ready for these 30 minutes.

And why is that? The answer is simple. Because we need to engage the community and get the social license to operate. And so if there is one thing that you cannot afford the luxury to miss, it's the stakeholder engagement. I cannot just pop up in a village with a bucket of mosquitoes on the assumption that I'm a scientist working for the public good. It will not take anyone a PhD to understand if we are respectful of their values or not. We need to engage the community and then co-develop the technology with them. And so for that, we've built our engagement strategy on the pyramidal structure, starting with the villages where we operate all the way to the top with the government officials. The engagement is done step-by-step. It’s done in an inclusive way and also is done in full transparency. Ladies and gentlemen, there is one more thing that needs to be done before gene drive can be released in the field in Africa.

That is capacity building. Gene drive holds a lot of promises, but it will not take us anywhere if we Africans aren’t enabled to run it on our own. Sadly, the technical platform in Africa is really very poor, and this has to be solved before we can really beat malaria. And so for that, we've set up in Burkina Faso a World Bank-funded center of excellence on vector-borne diseases, like malaria. And also with additional funds from the Gates Foundation, we are building a critical mass of next-generation scientists all over the continent to fill the knowledge gap and the know-how gap as well. In April 1969, a child was born in a remote village of Burkina Faso. Like any other child of the world, he had dreams and expectations. Sadly, however, as he came to learn, the place where you are born on this planet very often affects your perspective on life and may even set the path you need to walk through into your future.

That shouldn't be the case. We are all citizens of the world. Our dreams and aspirations should not be constrained by the place where we are born. And this is the reason why I became a scientist. To offer endless possibility to any child anywhere on this continent, so that they can see the future with hope. But there is no hope if you are cut short with malaria. But Target Malaria is here to fix that. A world free of malaria is our vision. And I will say, yes, we can. Thank you for your attention. (Applause)

How To End Malaria Once and for All | Abdoulaye Diabaté | TED

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Malaria has been a global public health issue for centuries, with millions of cases and deaths, particularly in Africa and Asia.

The disease is closely linked to poverty, with children and pregnant women bearing the highest burden.

Despite personal survival stories, such as the speaker's, malaria still claims the lives of many children today.

Tackling Malaria: The Challenge and Gene Drive Solution

Malaria is a complex disease involving the Plasmodium parasite, Anopheles mosquitoes, and humans, making effective intervention difficult.

Current strategies, including vaccines, bed nets, and treatments, are hindered by logistics and resistance.

Target Malaria is working on gene drive technology to control mosquito populations and disrupt the doublesex gene, which affects female fertility, with the aim of halting malaria transmission.

Gene-Driven Mosquitoes: A New Approach to Malaria Control

The modified gene targets female mosquitoes, causing those with two copies to become infertile and exhibit both male and female characteristics.

This suppression strategy aims to reduce the mosquito population and, in turn, lower malaria transmission.

While the technology shows promise, it has never been tested in Africa and raises concerns about resistance, cross-border issues, environmental impact, and community acceptance.

The gene of interest in the mosquitoes cannot self-propagate and will go extinct in a few generations.

The release process involves a step-by-step approach, starting with small cages in Europe and then testing in Burkina Faso before moving to open field releases.

Community engagement and stakeholder involvement are crucial for the success of the gene drive project, with a planned timeline of four to five years for preparation before the actual release.

Capacity Building to Combat Malaria in Africa

The technical platform in Africa is weak, hindering progress in malaria control.

A World Bank-funded center of excellence on vector-borne diseases is being established in Burkina Faso, with additional support from the Gates Foundation to train next-generation scientists.

The speaker, inspired by their own upbringing, is dedicated to offering hope and opportunities to children in Africa, with a vision of achieving a world free of malaria.