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Zapping mosquitoes from the inside out

While chemical mosquito population control measures have been used with some degree of success, they are toxic to other insect populations and to the health of humans. A different angle of defense has emerged, which is genetic modification of the mosquito itself, making it transgenic. Transgenic mosquitoes are unable to transmit a pathogen, such as malaria, due to their altered genetic makeup. (DoD photo) While chemical mosquito population control measures have been used with some degree of success, they are toxic to other insect populations and to the health of humans. A different angle of defense has emerged, which is genetic modification of the mosquito itself, making it transgenic. Transgenic mosquitoes are unable to transmit a pathogen, such as malaria, due to their altered genetic makeup. (CDC photo)

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Mosquitoes aren’t just annoying at summer barbecues. In many parts of the world, they carry pathogens for Zika, dengue, yellow fever, and the most devastating of mosquito-borne diseases, malaria. According to the Centers for Disease Control and Prevention, 440,000 people died in sub-Saharan Africa in 2016 from malaria, contracted from the bite of infected female Anopheles mosquitoes. Malaria causes severe chills, high fever, profuse sweating, and other flu-like symptoms, and if left untreated, can lead to death. Protecting U.S. military personnel who continue to serve in this part of world is critical.

The Department of Defense Armed Forces Pest Management Board has curated various personal protective repellant systems for deployed service members: permethrin-treated uniforms, application of insect repellants such as DEET and Picaridin, permethrin-impregnated bed nets, and prescribed antimalarial medication. They also oversee the Deployed Warfighter Protection Research Program that studies how to mitigate a variety of insect threats to military personnel.

While chemical mosquito population control measures have been used with some degree of success, they are toxic to other insect populations and to the health of humans. A different angle of defense has emerged, which is genetic modification of the mosquito itself, making it transgenic. Transgenic mosquitoes are unable to transmit a pathogen, such as malaria, due to their altered genetic makeup.

The concept of transgenic mosquitoes has been around since the 1980s, although the first laboratory colony wasn’t developed until 1997, according to Dr. Marcelo Ramalho-Ortigao, associate professor of preventive medicine in the Department of Preventive Medicine and Biostatistics at the Uniformed Services University in Bethesda, Maryland. There are currently two methods used to control mosquito-borne diseases using transgenic mosquitoes. One is population replacement using a concept known as “gene drive” to spread anti-pathogen genes. The other is a population suppression strategy that reduces the number of mosquitoes that can pass on the pathogen.

So far, the idea of using transgenic mosquitoes to combat malaria has been tested in laboratory settings only. However, successful genetic modification of a particular species of mosquito, Aedes aegypti — known to spread the Zika, dengue, yellow fever, and chikungunya viruses — has been both laboratory and field tested by Oxitec, a United Kingdom-based company.

“This field of study and research has changed dramatically since the discovery and advent of the gene-editing technology known as CRISPR-Cas9, as the speed and the number of genes that can be targeted has increased,” explained Ramalho-Ortigao. Field tests of mosquitoes modified using the CRISPR technology are still in the research and development phase.

Because of the ethical ramifications of gene editing to alter mosquitoes or other species, this concept has always been controversial, Ramalho-Ortigao said. “Controversy and discussions with regard to applications, and especially how to control against unwanted effects, is critical for the advancement of science, especially with regard to transgenic technologies.” Government regulation by the Food and Drug Administration and the Environmental Protection Agency is a way to ensure studies do not deviate from their scientific goals, he added.

In addition to potentially proving a new tool in the fight against mosquito-borne diseases, “studies of insect transgenics also provide crucial training for the next generation of scientists who may be involved in cutting-edge research and possibly apply techniques they learned using mosquitoes or other insects as a model for higher organisms,” explained Ramalho-Ortigao. He pointed out that insects “share many common features with vertebrates with regard to gene expression, ability to mount an immune response to invading microorganisms and viruses, and certain behavioral traits.” Scientists may therefore be able to apply knowledge gained about insects toward organisms “higher in the evolutionary scale, including vertebrates,” he said.

Although humans may not miss mosquitoes if they were to be eradicated, our ecosystem would. “Mosquitoes play an important role as pollinators," said Ramalho-Ortigao. “Also, they are a food source for other insects, spiders, frogs, lizards, and birds.” He added that not all mosquitoes transmit disease and only females blood feed, which allows them to lay eggs. In fact, of the nearly 3,000 known mosquito species, only a fraction transmit diseases. Complete elimination could lead to the expansion of other species or an increase of the population of a species that is currently present in smaller numbers – creating a whole new bug problem.

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