It’s not just tourists who love the Sunshine State. Florida is also a paradise for mosquitoes, thanks to its year-round warm and humid climate. The inhabitants have always suffered from the plague spirits. However, which immigrated from the tropics, also reproduces magnificently there. And it is more than just annoying, because it can transmit viral diseases such as yellow fever, Zika, chikungunya and dengue fever. There are no drugs to deal with these sometimes deadly infections, one can only try to mitigate their symptoms.

Insecticides have been regularly sprayed for decades, not only in Florida to prevent disease outbreaks. Nevertheless, disease transmissions occur again and again. For example, Florida has already had 22 dengue cases for the current year. “Resistance to insecticides is increasing in many mosquito species worldwide. Some species are now multi-resistant,” says Marc Schetelig from the Institute of Insect Biotechnology at the University of Giessen, Germany. In addition, there are environmental concerns, as the widespread use of synthetic insecticides such as pyretroids and organophosphates is associated with the worldwide decline of insects.

Against this background, the United States Environmental Protection Agency and the state of Florida recently approved an experiment that is as sophisticated as it is controversial: the British company Oxitec, a subsidiary of the US company Intrexon, is allowed to release several million genetically modified yellow fever mosquitoes in the state. They are intended to drastically reduce the population of their wild counterparts.

Extreme birth control

Oxitec’s method is an extreme form of birth control: only male yellow fever mosquitoes of the PRODUCT strain OX5034 will be released. Two new genes have been added to their genetic material: DsRed2 is a marker gene that produces a fluorescent protein. When irradiated, the genetically modified larvae and mosquitoes light up in color, which allows the spread of the released animals to be controlled.

The gene tetracycline transactivator (tTAV) leads to the death of the female animals still in the larval stage, because the cell reads it so often that the associated tTAV protein accumulates so much that the cell machinery collapses – the animals die. This process can be suppressed by administering the antibiotic tetracycline to the larvae. Without such a switch, the animals were not be able to be reproduce in the laboratory.

Genetic engineering can be used to virtually snap out the female sex

In male animals, however, tTAV is not active because they read the gene differently, a process that biologists call gender-specific splicing. If OX5034 mosquitoes are paired with wild females, only the male offspring will survive. As the female population shrinks with each mating cycle, the mosquito population will decrease significantly over time.

“Basically, this is an environmentally friendly and very targeted method, because it is species-specific,” says Ernst Wimmer from the University of Göttingen.

750 million genetically modified mosquito males

Oxitec says it has already released more than a billion mosquitoes in the Cayman Islands and parts of Panama and Brazil since 2009. The populations of the wild yellow fever mosquitoes subsequently collapsed by more than 90 percent.

In Florida, more than 750 million mosquito males could be released by 2021. The experiment itself is unspectacular: employees deposit rearing boxes with a known number of eggs in predetermined locations and add water so that the insect males can develop. Humans do not come into contact with the GM mosquitoes, as the mosquito males cannot sting and feed on plant juice.

The method can be seen as a further development of the so-called sterile insect technique (SIT), which has been used in various insect species worldwide for about 70 years. Biologists sterilize bred insect males by radioactive radiation. Farmers release the sterile males in masses to displace the wild male species. If the females pair with the sterile males, they do not produce offspring and the pest population shrinks.

The classic SIT is a very successful method, which has been used to eradicate the tsetse fly on Zanzibar and which is still used daily in the fight against the Mediterranean fruit fly. Originally from Kenya, it has since spread across all five continents and is a dreaded pest in vegetable and fruit growing agriculture. “The largest breeding facility is located in Guatemala, where up to four billion males are bred every week. That’s about 20 tons of insects,” explains Schetelig. In the US, millions of animals are released daily at hotspots such as airports and ports to prevent outbreaks. In Europe, too, sterile Mediterranean fruit fly-men are released daily, and the breeding facilities are located in Israel and Spain.

The question is: What alternatives do we have?

Marc Schetelig

“The problem with this method is that some of the irradiated males are not completely sterile. However, the radiation dose cannot be increased arbitrarily, because the damage will increase. If the behavior of the factory males deviates from the norm, free-range females would not want to mate with them,” explains Wimmer.

Another catch is that the classic SIT cannot be applied as well to every insect species as with the example of the Mediterranean fruit fly. “You need a suitable system to be able to breed only males in masses,” explains Schetelig. This is where genetic engineering comes into play, with which the female sex can be virtually snapped out with genetic tricks such as the tTAV system.

Oxitec’s OX5034 mosquitoes differ from the classic SIT animals in one essential point: the OX5034 males used are just not sterile. They are supposed to inherit the female-killing tTAV gene to the next generation. This is desirable in order to reduce the population over the course of several mating cycles without the need to continuously release more males – which is absolutely necessary with the classical SIT. After a few generations, the OX5034 males disappear from nature, as the Mendelian rules take effect, i.e. only half of the male offspring inherit the OX5034 genome.

Oxitec’s release plans are met with mistrust by various environmental groups in Florida. In autumn 2019 a publication in the journal Scientific Reports had generated negative headlines worldwide: Oxitec’s transgenic mosquitoes would have spread out of control in Brazil. “The work was misleading,” says Wimmer, who is not alone in his criticism.

In Brazil, Oxitec’s experiments have a high degree of approval. The pressure of suffering from Zika and dengue infections is crucial, Wimmer says.

Arthur Marquis

With a background in dermatology and over 10 years of experience, Arthur covers a wide range of health-related subjects for the Scientific Origin.