Are we entering a new era of mosquito control?
These new methods, from parasites to gene editing, control mosquitoes without pesticides.
The global fight against mosquitoes and the diseases they carry is stalling.
For decades, the deployment of anti-mosquito tools, including insecticides and bed nets, helped alleviate the burden of diseases like malaria and dengue. But in recent years, progress has slowed, and even reversed, as mosquito populations evolve around these interventions. Climate change is stoking the spread of mosquito-borne disease too, as shifting temperatures expand skeeters’ range. Last year, the U.S. saw its first locally transmitted case of malaria since 2003, and this year, dengue is spreading in record numbers around the world.
“We have all these tools, medicines, bed nets, but the disease is still there,” says Lea Paré Toe, a social scientist with the non-profit Target Malaria in Burkina Faso. “That’s why we need research to come up with new tools that can boost elimination.”
That research is well underway—from efforts to enlist the help of common parasites to tinkering with mosquito genes. Some new tools are already in use, while others are still years from being approved by regulators. But all show promise and could play important roles in a new era of mosquito control that’s potentially easier on the environment than chemical pesticides.
Blocking transmission with a parasite
One promising new tool comes not from a lab, but from nature.
Wolbachia are parasitic bacteria that infect about half of all insect species. The parasite is so ubiquitous, in part, because it can manipulate host reproduction to its own benefit. Infected mothers pass Wolbachia down to all her female and male offspring. When those males mate with an uninfected female, the parasite essentially kills the eggs, hastening Wolbachia’s spread through the population.
Aedes aegypti mosquitoes aren’t naturally infected. But in 2009, entomologist Scott O’Neill and colleagues discovered that Wolbachia infection rendered mosquitoes largely incapable of transmitting many pathogens, including dengue, zika, and even malaria.
It’s still unclear how Wolbachia inhibits transmission. But that hasn’t stopped the World Mosquito Program, a non-profit headed by O’Neill, from developing and testing a mosquito control program that breeds Wolbachia-infected mosquitoes (by carefully injecting Wolbachia into eggs) and releases them into affected areas.
Since 2011, the program has released millions upon millions of mosquitoes in Australia, Indonesia, Brazil and 11 other countries in field trials. “We usually keep releasing until we get to a threshold of about 60 percent of mosquitoes having Wolbachia,” says O’Neill. “At that point, we stop and Wolbachia does the rest by itself.” In many regions, Wolbachia-mosquitoes can represent up to 90 percent of a population within several years, and don’t require future releases.
A 2021 field trial in Yogyakarta, Indonesia, Wolbachia mosquitoes helped drive down dengue cases and hospitalizations by 77 and 86 percent. In parts of Australia, “we’ve essentially eliminated dengue transmission,” said O’Neill.
Wolbachia likely won’t work everywhere, especially areas with extreme temperature swings, O’Neill says. It’s also difficult to inject millions of eggs with Wolbachia and spread them in communities. But a new study suggests drones could speed up distribution, showering up to 160,000 adult mosquitoes per drone from the sky.
Tweaking genes to shrink mosquito numbers
Other techniques take a more direct approach to either sterilize mosquito males or kill biting females before they reach adulthood.
Since the 1950s, researchers have tried sterilizing males with radiation and releasing them into the wild to fool females into mating, shrink the population and reduce disease transmission. But blasting skeeters with radiation can kill males before they get a chance to mate.
Now, researchers are using genetic engineering to target specific genes involved in fertility or viability. Oxitec, a biotechnology company based in the United Kingdom, has already released over one billion genetically modified mosquitoes in parts of Florida, Brazil, Djibouti and several other countries, in partnership with local governments.
The engineered male mosquitoes carry a self-destruct gene that prevents the female offspring that inherit it from surviving to maturity. The company uses the antibiotic tetracycline to disable the engineered gene, allowing Oxitec’s factory in Brazil to produce millions of engineered mosquitoes each week.
Field studies in Brazil suggest that Oxitec mosquitoes, which hatch by the thousands from egg-containing boxes, can crash Aedes aegypti numbers by up to 96 percent in less than a year in some neighborhoods.
Omar Akbari, a biologist at the University of California San Diego, is trying a different method, harnessing a gene editing tool called CRISPR-Cas9 to sterilize males. His team targets two genes, one involved in male fertility, and the other important for female viability. Combining these two genes produces only sterile males, which can be released at any life stage, including eggs. While this tactic hasn’t been tested in the field yet, Akbari says it could be simpler than Oxitec’s methodology, as it releases sterile males from the get-go and doesn’t require antibiotics.
The laws of genetic inheritance, whereby any gene has a 50 percent chance of getting passed onto offspring, set a speed limit on how quickly these genetic modifications can spread through a population. That requires continually pumping modified mosquitoes into an area, albeit at lower levels, to keep populations controlled, said Oxitec CEO Grey Fransden. “It turns into a maintenance operation to continue to defend an area.”
Some researchers are trying to engineer around those speed limits to produce a more permanent solution.
Supercharging evolution with gene drives
Gene drives are self-propagating genetic modifications that tip the scales of heredity, ensuring that a given gene gets inherited, even if only one parent carries it. Here’s how it works: Researchers insert the drive into a mosquito’s chromosome using CRISPR. The engineered mosquito mates and passes the drive on to its offspring. Then the drive quickly copies itself onto the offspring’s other chromosome. This biased inheritance can spread the drive — and any genes attached to it — like wildfire within a population.
Controlling a population with gene drive would only require introducing a relatively small number of modified mosquitoes, says Federica Bernardini, a researcher at Imperial College London who works with Target Malaria. Then, the drive takes over, infiltrating the entire population much faster than it would under the normal rules of evolution. “It makes them self-sustaining,” they say, a key benefit for rural areas with a lot of malaria cases but limited infrastructure.
Target Malaria’s researchers are currently investigating gene drives targeting a sex-determination gene called doublesex. Females with two copies of the tweaked gene can’t bite and don’t lay eggs, but males and females with only one copy are unaffected, allowing the alteration to spread rapidly. In 2021, the team demonstrated that their gene drive could spread through a population of about 800 caged mosquitoes quickly, ultimately collapsing the population of malaria-carrying Anopheles gambiae mosquitoes in less than a year.
Other researchers are taking aim at the parasite that causes malaria itself, not the mosquitoes.
“We’ve engineered the mosquitoes so that their genes attack the parasite as it’s developing in the mosquito, so they don’t become infected and they don’t become infective,” says Greg Lanzaro, a biologist with the University of California Malaria Initiative. This method avoids a potential ecological fallout of removing large numbers of mosquitoes from the food web, he says
Both research groups are planning field trials, in accordance with the World Health Organization’s guidance for testing gene drives. A key part of that framework is engaging with local communities, making sure they understand the technology and can voice their concerns before it gets deployed.
Gene drives’ power comes with great risk, and for that reason, they haven’t been deployed in the wild yet, as regulators grapple with this developing technology. Drives may uncontrollably spill outside of countries that approve their use, might not work as well outside of the lab, or may break down over time. But ultimately, only field trials will reveal gene drives’ true utility, and those are likely several years away.
All of these different technologies could shape the future of mosquito control. Gene drives may be a better fit for contained ecosystems, like islands, but not land-locked countries. Wolbachia could work in the tropics, but not in more temperate zones. Cities may tire of the expense of continually pumping out genetically-modified mosquitoes. And the insects’ potential to evolve resistance looms over all these tools.
“There is no silver bullet,” said Bernardini. “Any strategy, whether it’s novel or old-fashioned, will be needed.”
