Researchers have completed the first open-air study of genetically engineered mosquitoes in the United States. The results, according to the biotechnology firm running the experiment, are positive. But larger tests are still needed to determine whether the insects can achieve the ultimate goal of suppressing a wild population of potentially virus-carrying mosquitoes.
The experiment has been underway since April 2021 in the Florida Keys, a chain of tropical islands near the southern tip of Florida. Oxitec, which developed the insects, released nearly five million engineered Aedes aegypti mosquitoes over the course of seven months, and has now almost completed monitoring the release sites.
Based in Abingdon, UK, the firm reported the first results from the experiment during a webinar on 6 April, although it has not yet published the data.
Following the plan
Wild A. aegypti mosquitoes can carry viruses such as chikungunya, dengue, Zika and yellow fever, so scientists have sought ways to reduce their populations. Oxitec’s engineered males carry a gene that is lethal to female offspring. If all goes to plan, when released into the environment, the engineered males should mate with wild females, and their female offspring will die before they can reproduce. Male offspring will carry the gene and pass it on to half of their progeny. As each generation mates, more females die, and the A. aegypti population should dwindle.
To make sure the mosquitoes follow this scheme, researchers placed boxes of Oxitec mosquito eggs on private properties in the Keys and surrounded them with traps, covering a radius of more than 400 metres. Some traps served as egg-laying sites, and others caught adult mosquitoes.
The researchers found that the males that hatched from the eggs typically travelled within a one-hectare area around the release box — the same range over which wild A. aegypti fly. The engineered mosquitoes, which don’t bite, mated with the wild population, and wild females laid eggs in Oxitec traps, as well as in sites such as flower pots, rubbish-bin lids and soft-drink cans.
Oxitec researchers collected more than 22,000 eggs from the traps and brought them back to their laboratory to hatch under observation. The firm reported that all females that inherited the lethal gene died before reaching adulthood. (Researchers can determine this because mosquitoes carrying the lethal gene fluoresce under certain light.)
Furthermore, the team found that the lethal gene persisted in the wild population for two to three months, or about three generations of mosquito offspring, and then disappeared. No mosquitoes carrying the lethal gene were found beyond 400 metres of the release points, even after several generations. Oxitec monitors the sites for ten weeks after the last lethal gene-carrying mosquito is found.
“I like the way they’re going about it,” says Thomas Scott, an entomologist at the University of California, Davis. “They’re doing it in a systematic, thoughtful way. So I’m encouraged, but they have a lot of work ahead of them,” he says.
The pilot study was not intended to determine how well the method suppresses the wild population. Oxitec plans to gather that data in an extension of the Florida Keys study. It first needs approval from state regulators, but hopes to begin soon. The company plans to release mosquitoes at a second study site in Visalia, California, where it is building a research and development facility.
Quashing outbreaks
But these expanded studies will not assess whether Oxitec’s method reduces transmission of dengue or other viruses carried by A. aegypti. “They’re not going to be able to do a trial to show that it actually has a public-health impact,” Scott says. “There’s not enough Aedes-transmitted viral infection in the Florida Keys,” or anywhere in the continental United States to do that kind of study, he says. To run such an experiment, the company would have to invest in a controlled trial elsewhere, and run the study like a clinical trial, which would be enormously expensive.
Disease outbreaks can occur even when A. aegypti populations are low, so reducing the mosquito population won’t necessarily translate into disease suppression anyway, Scott adds. “It’s just not that simple.”
Suppressing A. aegypti also won ’t reduce the need for pesticides. A. aegypti makes up only about 4% of the mosquito population in the Keys. The black salt marsh mosquito (Aedes taeniorhynchus) — more of a nuisance than a disease vector — probably represents about 80% of the mosquito population on the islands.
Still, the Florida Keys Mosquito Control District (FKMCD), the local abatement group, supports Oxitec’s trials. “We’ve dealt with multiple disease outbreaks, so we’ve got to do everything we can to protect our people down here and the economy,” says Andrea Leal, executive director of FKMCD. That means trying new things, she says. “We’re looking at any tool that could be helpful.”
The Keys experienced an outbreak of dengue fever in 2010, with 68 locally transmitted cases, and again in 2020, with 72 locally transmitted cases, according to FKMCD. In 2017, the group worked with MosquitoMate, a biotech firm in Lexington, Kentucky, to release A. aegypti males that were infected with the bacterium Wolbachia pipientis. The lab-grown males mate with members of the wild population to produce eggs that do not hatch.
In 2020, FKMCD approved Oxitec’s trial after seeking community input. In a 2016 referendum, 31 out of 33 precincts in Monroe County, where the Keys are located, voted in favour of the project, although some local residents and environmental groups protested the plan. It’s particularly important, Scott says, that FKMCD and Oxitec have made an effort to interact with the community, especially “for something as controversial as genetically modified mosquitoes”.
The US Environmental Protection Agency (EPA) and the state of Florida also gave Oxitec permission to run the 2021 project. The firm’s 2022 projects in Florida and California were approved by the EPA in March, and the company awaits permission from both states.