Oxitec offers promising data even though the company has yet to be approved by the California Department of Pesticide Regulation to release their “friendly” mosquitoes
VISALIA – Biotech company Oxitec is buzzing around Visalia, with the hopes of releasing their genetically engineered mosquitoes in Tulare County.
Oxitec has one more hurdle to jump over in order to release their “friendly” Aedes aegypti mosquitoes in Tulare County, and that’s to gain the approval of the California Department of Pesticide Regulation (DPR). Though their attempts to release their GE mosquitoes in California have been met with both supportive and hesitant reactions from different state agencies and environmental groups, Oxitec’s Dr. Kevin Gorman said the technology has been researched and reviewed with “much scrutiny,” despite claims that the mosquitoes are ineffective or hazardous.
“We have a biological approach to managing pest insects, and the biological approach is a mating-based technology. It’s very targeted, it only affects the species that [they’re] mating with,” Gorman said. “Not only is it environmentally safe, it’s effective.”
The male GE mosquitoes from Oxitec have been engineered with a self-limiting gene, and this gene infects wild female mosquitoes to prevent them from reproducing female offspring. This leaves only male mosquitoes in the gene pool, according to Gorman. Female mosquitoes are targeted since they are the only ones that bite, and therefore capable of transmitting diseases. The engineered males will only mate with Aedes aegypti females, and do not leave an environmental footprint, according to Gorman. The release of these mosquitoes is supposed to reduce the natural population of the invasive mosquito, which are known to carry diseases such as dengue, chikungunya, Zika, yellow fever and others.
“There are ways of modifying mosquitoes or other insects so that they overtake a population, and once they’re released it’s a bit like a genie out of a bottle — you can’t put them back in — but that’s not us,” Gorman said. “What we have is technology that dies out, it’s destined to die, and that means that in just a few weeks and a few generations after we’ve released our mosquitoes, they’re gone.”
The GE mosquitoes also have a fluorescent marker gene which enables them to be distinguished from invasive mosquitoes for effective monitoring. The self-limiting gene cannot establish istelf in the ecosystem long term and does not impact non-target species, according to Gorman.
SUPPORT FROM SOME
Oxitec’s technology started off in 2002 with mosquitoes labeled OX513A, and the original mosquito killed off both male and females, according to Gorman. The GE mosquito was modified in 2018 and named the OX5034, so that only the female offspring were killed off. This modification allows the technology to be more targeted and sex-specific, according to Gorman. This also allowed Oxitec to release eggs into the environment, so that when they hatch, only male offspring survive and are released. It also eliminates the need to manually determine the gender of the mosquitoes, and risk potential release of females into the wild due to inaccurate sexing.
“[We have] received commercial approval in Brazil,” Gorman said. “There’s no requirement for us to have an excess extra permit or license, so we can release it anywhere we want [in Brazil], because it’s deemed as safe and effective.”
Four years after the second generation of Oxitec’s GE mosquitoes were developed, there was a risk assessment done by the Environmental Protection Agency (EPA), where they partnered with the Center of Disease Control (CDC) to see if the introgression of the GE mosquitoes would create a more robust offspring with wild populations. Their results said that a robust version was unlikely, and they had also found that introgression did not make the population more resilient to insecticides as the natural population, according to the EPA risk assessment. The testing from the EPA and CDC have found little, if any, risk that the GE mosquitoes present.
Gorman mentioned that Oxitec’s technology is a more holistic approach to lower the population of the Aedes aegypti in the environment. That’s especially true since this species of mosquito is becoming increasingly resilient to public health pesticides, according to the Mosquito and Vector Control Association of California (MVCAC), who stated this in the EPA’s risk assessment. Additionally, Norman Leppla from the Integrated Pest Management University of Florida, has said that these mosquitoes were even becoming resistant to pyrethroids, which are the most commonly used type of mosquito insecticides.
CONCERN FROM OTHERS
In 2015, a few years before the second generation of Oxitec’s Aedes aegypti mosquitoes were developed, a Yale researcher named Jeffrey Powell conducted a peer-reviewed study on the first version of Oxitec mosquitoes, the OX513A, that were released in Brazil that year. In the study, there was data that showed introgression, which is when one species transfers genes to another, between the natural population of mosquitoes and the GE mosquitoes, according to Powell. Gorman said that this introgression was true, but he said that only “wild” and natural genes were being passed to the wild population, not the transgenes, which are the genetically modified genes.
Powell said that this research was done using a genotyping tool that allowed the researchers to look at genes across the entire genome efficiently and rapidly. The tool was used on both the target population and GE release strain. At first, the target population and GE release strain were genetically distinct, but when the researchers returned after the releases were done, they found genotypes in the natural population that were not there before.
This study was mentioned by the California Food and Safety Department (CFSD) and environmental advocacy group Friends of the Earth, who pushed for more review to be made before Oxitec could release GE mosquitoes in California because of the fear that introgression would lead to a more robust version of the mosquitoes offspring. Powell had questioned if the introgression could lead to hybridized, robust offspring, and is actually very common, Powell said. This question, however, was not the main premise of the study, Powell said, and also pertains to the version of mosquitoes that were released during that time, which was a year before Oxitec released their second generation of mosquitoes. Gorman also said that the introgression was expected, but minimal.
Powell’s questioning of the data is based on the idea that is common in genetics, which is, if you cross two different strains of a species then the offspring comes out stronger. He used agriculture as an example of this idea, and said that if you cross two different strains of a crop, the hybrids are usually stronger than the parent lines. Since the strain released in Brazil had genes from Cuba and Mexico Aedes aegypti, this would create a three-way hybrid, which is why Powell had questioned the outcome of a stronger hybrid offspring.
SOON TO BE BUZZING
The Department of Pesticide Regulation will be the last step for Oxitec before they can begin to release it in Tulare County. The DPR’s review of Oxitec’s technology includes a scientific evaluation and a public comment period, which has proven to take some time already. The DPR has already delayed the release of the mosquitoes for at least another year, as the mosquitoes were supposed to be released in June, but since the reviewing process can take several months, Oxitec will have to wait until next June to release their technology.
The U.S. Environmental Protection Agency approved the release of the mosquitoes in Tulare County, Calif. as well as Monroe County, Fla. on March 7, 2022 after a 15-month scientific evaluation process, but is still awaiting approval from the DPR. The department ended a 15-day public comment period on April 19 but confirmed in an email to The Sun-Gazette “that the evaluation and review process will take at least several months.”
California regulators will spend the next few months evaluating Oxitec’s second study in the county. DPR said its review of the research authorization application will entail a rigorous scientific evaluation, consultation with the California Department of Public Health, Tulare County Agricultural Commissioner’s Office, the Delta Mosquito and Vector Control District and consideration of public comments and input.
DPR must approve a research authorization application before an unregistered pesticide can be field tested in the state. DPR toxicologists, entomologists, microbiologists, ecotoxicologists and other department scientists will review the application, research design, scientific studies and additional information.
Since first being detected in 2013, Aedes aegypti has rapidly spread to more than 20 counties throughout the state, increasing the risk of transmission of dengue, chikungunya, Zika, yellow fever and other diseases. While chikunga, yellow fever and Zika are typically not associated with severe illnesses, dengue can lead to shock, internal bleeding, and even death, according to the CDC.
California would be only the second U.S. state after Florida where GE mosquitoes could be experimentally released. Florida was the first state to get involved with Oxitec’s pilot program, with the EPA approving the release of the GE mosquitoes on March 8, 2022 and by the Florida Department of Agriculture and Consumer Services in May. The Florida Keys Mosquito Control District continued the release of the mosquitoes on Sept. 16. This is the third phase of mosquito releases, with the first release being in May. Oxitec reported that the number of GE mosquitoes that will be released across all three of Florida’s 2022 phases is estimated to be seven million.
“Florida just happens to be one of the most plagued states in the US on this particular mosquito, they suffer more disease from this mosquito than anywhere else that’s locally acquired, and they have it pretty much year round,” Gorman said.