Why Consider Using A Genetically Modified Mosquito?

By now, most of us have heard of mosquito-borne diseases caused by pathogens such as chikungunya, dengue and Zika virus. The primary vectors of these diseases, Aedes aegypti and Aedes albopictus mosquitoes, can be difficult to control due to their day-active nature in urban and suburban environments. Some scientists and disease control officials have proposed using the mosquito itself to find and eliminate other mosquitoes, as an alternative or in addition to insecticides and/or constant campaigns to reduce sources of standing water in containers where these mosquitoes lay their eggs.

Modified mosquitoes may be considered a tool in the toolbox for mosquito control, part of an integrated mosquito management approach. Regular surveillance of mosquito populations, targeted mosquito control with larvicides and/or adulticides, insecticide resistance monitoring and preventing mosquito bites using repellants, etc., are still important and necessary aspects of mosquito control programs that should continue.

How are mosquitoes modified before release?

Oxitec, Ltd. (Oxford Insect Technologies) has developed a genetically engineered Aedes aegypti (OX513A) strain to suppress wild Aedes aegypti populations in areas where mosquito-borne diseases such as chikungunya, dengue and Zika are prevalent. This technology involves modifying mosquito eggs to contain a protein called “tetracycline repressible activator variant” that prevents mosquitoes from making it to adulthood, unless they are regularly fed an antidote of tetracycline. Mosquitoes are regularly fed the antidote when they are being produced in large numbers for field trials. Upon release into the environment, the protein becomes active, as they are no longer being fed the antidote.

Other groups have introduced a bacteria called Wolbachia pipientis (wMel strain) into Ae. aegypti that may lessen a mosquito’s ability to transmit dengue and Zika virus, hence reducing vector competence. This bacteria can be passed down through generations. Wolbachia pipientis is also being used to infect laboratory-reared Ae. aegypti males. When the males mate with wild females, the females become sterile. This is not a genetic modification. Instead, it is an alteration of the mosquito, as it does not naturally contain Wolbachia. Different strains of Wolbachia may also be used, depending on mosquito species and population.

What Happens When Modified Mosquitoes Are Released Into The Environment?

Oxitec’s methods include separating male and female pupae by size. Only males, which are smaller than females, are released into the environment. Male mosquitoes do not blood feed (only female mosquitoes blood feed), as they only feed on plant nectar. Once the male mosquitoes are released into the environment and are no longer fed the antidote, the protein becomes active again.

Genetically modified male mosquitoes mate with wild female mosquitoes of the same species; however, the larvae that hatch from eggs of affected females do not survive to adulthood. Eventually, this lack of adult mosquito emergence suppresses abundance and lowers the risk of disease. Genetically modified male mosquitoes need to have similar fitness and survival rates as wild male mosquitoes in order to make them competitive for wild females. Once modified mosquitoes are released and are successfully integrated into wild mosquito populations, suppression of mosquitoes does not happen immediately. Hence, this technique would not be the sole control method used in an outbreak situation, but could potentially be used in conjunction with other methods.

In the separate Wolbachia (wMel strain) method that is not a genetic modification but an introduction of a bacteria into mosquitoes, large numbers of male and/or female mosquitoes containing the bacteria can be released into the environment. The goal with some Wolbachia research is not to suppress mosquito populations, but to increase the number of mosquitoes that contain the Wolbachia bacteria, which reduces the mosquitoes’ vector competence. Since this technique requires that adult (blood feeding) female mosquitoes be released into the environment, this method may not be widely accepted by the public.

Wolbachia pipientis is also being used to infect Ae. aegypti males which, when released, mate with wild females that do not contain Wolbachia. Due to cytoplasmic incompatibility, the non-Wolbachia containing eggs that contact Wolbachia-containing sperm do not develop properly. The Wolbachia-infected females cannot produce viable eggs and this eventually suppresses mosquito abundance. However, if Wolbachia-infected males mate with (compatible) Wolbachia-infected females, the eggs are viable and can promote mosquito abundance.

Are Genetically Modified Mosquitoes Safe For The Environment?

In the Oxitec method, the protein that is produced in the genetically modified mosquito causes the mosquito to die by preventing other natural processes from occurring in the mosquito. If predator animals eat genetically modified mosquitoes, the modified mosquito proteins are digested and do not harm the animal.

On August 5, 2016, the U.S. Food and Drug Administration (FDA) released its Environmental Assessment (EA) and a Finding of No Significant Impact (FONSI) that states releasing these genetically modified mosquitoes will not have any significant environmental impacts. This FDA finding means that Oxitec can move forward with developing partnerships and approvals at local, state and federal levels to plan a potential field release of these mosquitoes in the United States.

Wolbachia is regulated by the Environmental Protection Agency (EPA) and is considered a biopesticide. More information about Wolbachia can be found here.

Currently, it is unknown what would happen to co-habiting Aedes albopictus mosquitoes after a decline in Aedes aegypti populations after a release of genetically modified mosquitoes. Aedes albopictus is also a vector of chikungunya, dengue and Zika viruses, but is implicated as a secondary vector primarily due to its opportunistic blood feeding habits (it feeds on whatever host is available), while Aedes aegypti primarily blood feeds on humans.

Have Any Genetically Modified Mosquitoes Been Released In The U.S.?
So far, Oxitec has completed field studies in Brazil, the Cayman Islands, Panama and Malaysia. Now that the FDA has released the EA and FONSI, it is possible that a field trial will move forward in some parts of Florida.

It will likely take some time for mosquito production facilities to be developed in the U.S. For instance, a 5,000 square meter production facility was recently developed in Brazil where 60 million genetically modified males per week can be produced.

For the separate Wolbachia method, field trials of Ae. aegypti containing Wolbachia are being carried out in Australia, Brazil, Colombia, Indonesia and Vietnam. Mosquitoes containing Wolbachia have also been released in Kentucky, California, and New York.

Are There Any Other Genetically Modified Mosquito Species Being Studied?

Research is being conducted on similar genetic modifications for suppressing a primary vector of the malaria protozoan, Anopheles gambiae; however, this is still a developing field. Other Wolbachia-containing mosquitoes that have been tested include Aedes polynesiensis and Aedes albopictus.

Dr. Stephanie L. Richards is an Associate Professor of Health Education and Promotion in the Environmental Health Sciences program at East Carolina University. She received a B.S. in Biology and M.S. in Environmental Health from East Carolina University. She completed her Ph.D. in Entomology with a minor in geographic information science at North Carolina State University. She completed her post-doctoral work in Arbovirology at University of Florida, Florida Medical Entomology Laboratory.