New research from the Debug project reveals the origin and movement of the mosquito Aedes aegypti—which could help disease control efforts
Authors: Dr. Jacob Crawford, Staff Scientist, Debug Dr. Bradley White, Director, Debug
The Global Dengue Threat
More than 4 billion people—half of the world’s population—are at risk of contracting dengue, a mosquito-transmitted disease, each year. And global cases are surging: according to the World Health Organization, reported instances of dengue have increased eight-fold in the past 25 years, from 500,000 in 2000 to a historic high of more than 14.6 million in 2024. Severe dengue can wreak havoc on the human body, causing sickness and even death.
While more than 3,500 species of mosquito exist, the Aedes aegypti mosquito is responsible for almost all cases of dengue. Unfortunately, there is no available vaccine that can provide comprehensive protection from the disease. As a result, the only way to limit transmission of dengue and other viral diseases transmitted by this mosquito species, including Zika and chikungunya, is by controlling the Aedes aegypti population itself.
The Debug team and academic colleagues spent the past several years putting together the first comprehensive genomic database that helps to catalogue the history of Aedes aegypti migration across the world and the genetic mutations that occurred along the way. These findings represent a major advancement in our knowledge of Aedes aegypti genomics and our mission of eliminating disease-carrying mosquitoes: providing a platform for both optimizing the implementation of existing vector controls tools and developing novel interventions.
We recently published our research in Science, along with the datasets we used to inform our work, in the hopes that other people working on controlling mosquito-borne illnesses may also benefit from these discoveries.
From the Forest to the City
Historically, Aedes aegypti was only found in African forests, breeding in tree-holes and feeding on non-human primates and other animals. While these forest populations still exist, over the past 500 years, a form of Aedes aegypti has adapted to specialize on humans—breeding in artificial water sources and feeding nearly exclusively on people. The human-specialized form has invaded almost the entirety of the tropical and subtropical world, with more recent incursions into temperate areas as well.
An organism’s genome can serve as a historical record of sorts, showing, for example, when a species’ population size may have changed and documenting migration patterns. In order to better understand the history of Aedes aegypti invasion, we sequenced the genomes of 1,206 individual mosquitoes from 73 locations across every continent except Antarctica, including both animal-preferring and invasive, human-preferring populations.
To collect some of the samples, our colleagues set up oviposition cups (i.e. artificial containers holding water) across forests and cities and waited for mosquitoes to lay eggs in the water. Because it’s impossible to identify eggs in the field, our colleagues brought all the eggs they gathered back to the lab for molecular testing.
Debug collaborators Dr. Noah Rose (UC San Diego) and Gilbert Bianquinche collecting Aedes aegypti eggs in Senegal for the study.
The team then sequenced the DNA of these mosquitoes on the Illumina platform and used Google Cloud’s compute power to map the billions of sequencing reads to the genomes of these mosquitoes, identifying millions of common and rare mutations. Demographic analyses based on this mutation database allowed us to pinpoint which regions of the genome were shared between populations, helping to unravel the routes that Aedes aegypti traveled as it invaded the globe and the approximate dates of these migrations.
Mastering Mosquitoes’ Movements
We found over 141 million mutations in these genomes that tell us about how Aedes aegypti has changed and moved over time.
We discovered strong evidence, in agreement with historical records on disease occurrence, that this species of mosquito migrated from Africa to the Americas \~350 years ago, almost certainly on ships carrying enslaved people. Approximately 100 years after this migration, the American population of the Aedes aegypti exploded in size and rapidly invaded the rest of the tropical world—including the Mediterranean basin, Asia, and Australia.
We also found strong evidence that this invasive form of Aedes aegypti has returned to Africa, helping to explain the recent, unprecedented urban dengue outbreaks in the region. These “back-to-Africa” populations harbor insecticide resistance genes selected for outside the continent, making control of the mosquitoes all the more difficult.
The Implications for Global Health
The Debug project is developing novel technology, powered by artificial intelligence, to raise and release sterile male mosquitoes in order to decrease populations of the ones that carry disease. This recent body of research has the potential to help us accelerate the process of introducing sterile Aedes aegypti into the regions that most urgently need population suppression.
Adult Aedes aegypti mosquitoes in a Debug cage being prepared for backcrossing
Whenever we release sterile males into a new area, it can take up to nine months to backcross our sterile lines with locally caught mosquitoes to ensure we are releasing Aedes aegypti that genetically matches the local population. The new dataset helps us to determine over what geographic region a single genetic line can be released - for example, our research found the same genetic line of the species could be released across multiple countries in South East Asia - which allows us to begin releases quicker and make the sterile male manufacturing process more efficient. We hope that by publicly releasing our dataset, we can provide a unique platform for researchers to develop new tools in the ongoing fight against dengue, Zika, and other illnesses spread by Aedes aegypti.
As we continue to develop technologies and methods to target disease-carrying mosquitoes, we’re partnering closely with scientists, communities, and governments around the world. If you’re interested in collaborating with our team, please reach out to partners@debug.com
The World Mosquito Program (WMP) of Monash University and Debug by Alphabet announced today that they are teaming up to explore a collaboration to deploy automated releases of Wolbachia Aedes aegypti mosquitoes to combat mosquito-borne diseases. This collaboration will leverage WMP's proven Wolbachia replacement method and Debug's proprietary rearing and release technologies to rapidly scale programs that reduce the transmission of diseases such as dengue, Zika, chikungunya, and yellow fever.
WMP has been at the forefront of innovative approaches in Wolbachia replacement programs globally. This safe and sustainable approach has been shown to significantly reduce the ability of mosquitoes to transmit viruses. A study published in the New England Journal of Medicine showed a 77% reduction in dengue incidence in areas where Wolbachia was deployed in field trials conducted by WMP in Yogyakarta, Indonesia[1]. Further results in Colombia’s Aburrá Valley and the Brazilian city of Niterói show the lowest number of dengue cases in more than 20 years, following WMP’s Wolbachia releases.
Debug has developed proprietary end-to-end technology that includes automated rearing robots, AI powered visual sex sorting systems, data surveillance, and release platforms to efficiently deploy Wolbachia suppression programs in several countries. Debug’s automated release platform on vehicles enables coverage of large areas more effectively than manual methods while leveraging software for targeted distribution.
The collaboration between WMP and Debug brings together two global leaders in the fight against vector-borne disease. By combining the respective expertise and compatible values on global health impact, the collaboration aims to accelerate progress of current and future Wolbachia programs to reduce the global burden from mosquito-borne diseases.
Linus Upson, founder of Debug, shared “We are excited about the opportunity to partner with WMP. In addition to utilizing the technology we have built to deliver Debug's proven Wolbachia suppression programs, we can provide our proprietary technology to deliver automated releases in WMP’s Wolbachia replacement programs worldwide. This is an exciting moment to unify groundbreaking biological and technological achievements to make a global impact.”
Scott O’Neill, CEO and Founder of the World Mosquito Program, said “Debug’s automated release technologies have the potential to significantly increase the speed and efficiency of our Wolbachia releases, accelerating our goal of protecting as many people as possible worldwide.”
Kieran Walters, Executive Director of Strategy & Partnerships of the World Mosquito Program, shared “We are thrilled to form an alliance with Debug to combat one of the biggest global health threats of the 21st century. By combining our technologies, we can deliver an integrated solution to protect vulnerable communities from mosquito-borne diseases on an unprecedented scale.”
The World Mosquito Program (WMP) is a not-for-profit group of companies wholly owned by Monash University, Australia, that works to protect the global community from mosquito-borne viral diseases such as dengue, chikungunya, Zika and yellow fever. After effectively eliminating transmission of these viruses from Australia, WMP has expanded to now be working in 16 countries across Asia, Oceania and the Americas, protecting more than 13.5 million people. For more information, please visit World Mosquito Program.
Wolbachia – a common bacterium found in about 50 percent of insects – is introduced in the Aedes aegypti mosquitoes that transmit dengue, chikungunya, Zika and yellow fever. The Wolbachia bacterium prevents the Aedes aegypti mosquitoes from transmitting these diseases.
The Wolbachia mosquitoes are then released in areas where mosquito-borne viruses are endemic. As they breed with wild mosquitoes, the number of Wolbachia mosquitoes grows over time until it remains high without the need for further releases.
Unlike other measures against mosquito-borne diseases, the Wolbachia method is safe for people, mosquitoes and the environment, and offers a once-off, long-term and self-sustaining solution to control the spread and impacts of dengue, chikungunya, Zika and yellow fever.
[1] Source: Adi Utarini et al “Efficacy of Wolbachia-Infected Mosquito Deployments for the Control of Dengue” The New England Journal of Medicine, Vol 384, No 23, June 2021 (link)
Debug is an Alphabet project that has developed proprietary technology to automate the rearing, sorting, and release of millions of non-biting, non-GMO, sterile male mosquitoes at scale for Wolbachia suppression programs. The end-to-end technology includes automated rearing robots, AI powered visual sex sorting systems, and data surveillance and release platforms to optimize efficiency and performance. Debug releases mosquitoes into targeted areas identified using ongoing surveillance.
Alex Jackson
Global Editorial & Media Relations Manager
alex.jackson@worldmosquito.org
Press and Media Relations
press@debug.com
Author: Yanni Yoong (Sr Program Mgr), Evdoxia Kakani, PhD (Staff Scientist), Monica Tsai (BD)
Following positive results from release of male Wolbachia-carrying Aedes aegypti in Singapore, we are happy to announce that Debug is supporting the expansion of Project Wolbachia in Singapore to cover 5 new residential sites to increase Project Wolbachia’s coverage from 350,000 households in 2023 to 480,000 households by Q1 2024 - an increase from 26% to 35% of households in Singapore.
Results from NEA’s Project Wolbachia – Singapore
Aedes aegypti mosquito populations in the existing study sites of Bukit Batok, Choa Chu Kang, Tampines (releases done by Debug by Verily since 2018), and Yishun have generally fallen by more than 90 per cent. Data from 2019 to 2022 indicates that residents living in areas with at least one year of releases were up to 77 per cent less likely to be infected with dengue.
Results from Debug’s release areas.
The heatmaps in Tampines and Marine Parade below show the “eraser effect” where releases of male Wolbachia-Aedes mosquitoes has decreased the dengue risk over time.
Source: NEA website
The increased capacity for Project Wolbachia from 7 million in 2023 to 11 million male Wolbachia-Aedes mosquitoes produced and released weekly is made possible by Singapore’s National Environment Agency (NEA) and its collaboration with Debug. By the end of Q1 2024, Debug will be producing and releasing more than 6 million male Wolbachia-Aedes mosquitoes per week for Project Wolbachia in Singapore .
Debug has been using its proprietary automation technology for the production, sex-sorting, and release of male Wolbachia-Aedes mosquitoes at the Tampines and Marine Parade study sites since 2023, following a collaborative research from 2018 to 2023.
Author: Jo Ohm, Scientist
We are excited to announce that the Verily Debug team is starting a collaboration with the BugOut program on Virgin Gorda in the British Virgin Islands. BugOut is a community-driven vector control initiative with the mission to reduce Aedes aegypti mosquitoes in the Territory. Aedes aegypti is invasive in the BVI and is both a vector of dengue, Zika and chikunguyna diseases, and a significant nuisance pest. The BugOut program is managed by Green VI, a BVI-based non-profit that works on environmental programs including waste management and environmental education.
BugOut’s aim to reduce Aedes aegypti mosquitoes ties in with Green VI’s other environment-focused initiatives, and piggybacks off the waste management effort to clean up neglected containers and piled trash that become breeding grounds for mosquitoes. Through targeted education, data-driven field work, and a consistent community presence, Green VI’s BugOut has successfully reduced mosquito breeding sites by 50% over the past 5 years. Debug is partnering with BugOut to launch the next phase of their program to further reduce Aedes aegypti mosquitoes using a Wolbachia-based incompatible insect technique (IIT). We are excited to be on board and looking forward to working on a unique and synergistic approach to mosquito control.
The Debug-BugOut partnership is launching as BugOut Wolbachia and combines Debug’s expertise in Wolbachia-male releases with BugOut’s ongoing efforts to rid the community of larval breeding sites. We will use our combined sets of tools to suppress Aedes aegypti on BVI in a way that follows Green VI’s environmentally-conscious and community-driven mission.
We will spend the next several months supporting Green VI’s BugOut team and their community representatives as they evaluate how to integrate a Wolbachia-male Aedes aegypti release program into their toolkit. Our BugOut Wolbachia collaboration started collecting data on the existing mosquito population on Virgin Gorda in February 2022. We have begun engaging with the community to share knowledge of how Wolbachia works and how it can be used to reduce mosquitoes and hopefully mosquito-borne disease in the BVI. We have also been working with the community on preliminary studies of released Wolbachia male mosquitoes to evaluate their ability to survive and disperse in the field. Virgin Gorda will be the first island in the BVI to pilot the BugOut Wolbachia program as we learn and adapt our methods to match the unique needs of the local community and mosquito population before potentially scaling to other parts of the Territory.
On September 15, the Debug team welcomed Singapore Prime Minister Lee Hsien Loong to our operations in Singapore, as part of his tour of the National Environment Agency (NEA) - Environmental Health Institute (EHI) Mosquito Production Facility. In addition to ongoing threats from Covid-19, dengue remains a top priority in Singapore, and his tour highlighted the importance of developing novel tools such as Project Wolbachia – Singapore to prevent the spread of dengue.
Prime Minister Lee saw first hand some of the tools that have enabled the success of Project Wolbachia – Singapore, in which Verily has partnered with the NEA-EHI since 2018. As part of the program, Verily has released male Wolbachia-carrying Aedes aegypti mosquitoes in parts of Tampines town and has achieved a greater than 90% reduction in mosquito population, resulting in 65-80% reduction in dengue cases.
We were honored to demonstrate our technology to Prime Minister Lee and Mrs. Lee, who joined him on the tour. Together they visited our Sex Sorting Room, currently housed within the NEA-EHI Mosquito Production Facility and took a deep dive into understanding our mosquito sex-sorting technology, which has been successfully used in Debug Fresno and Debug Innisfail to separate male and female mosquitoes using a computer vision algorithm and artificial intelligence.
We are excited to continue to deploy our engineering and scientific capabilities to support NEA-EHI in scaling up production, sex sorting and release of male Wolbachia-carrying Aedes aegypti mosquitoes over the years to come.
Yanni Yoong, Program Manager, Debug; Hyegi Chung, Country Lead, Verily
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