Bzzzz… here come the kamikaze mosquitoes

Home Technologist 02 Bzzzz… here come the kamikaze mosquitoes

In an effort to combat dengue fever, Brazil has authorised the dissemination of a transgenic insect. Now the question is: will the critters do their job?

Photo of an Aedes aegypti mosquito

Giving sterile males more mojo

Dengue fever is not the only disease spread by A. aegypti. The mosquito also transmits Chikungunya.

In the wake of a 2006 epidemic that infected more than 30 per cent of the population of the Indian Ocean island of Réunion, the French Institute of Research for Development (IRD) launched a project to fight the mosquito vector.

Due to the controversy surrounding genetic engineering in France, IRD chose a non-transgenic approach: sterilising males by irradiation.

This had a major drawback: irradiated males are not sexually competitive. The IRD team succeeded in optimising the X-ray dosage to avoid the problem.

“In the laboratory, the irradiated males are sterile and just as competitive as their wild brethren,” says Louis Clément Gouagna, project manager at IRD.

A small-scale pilot project to release the males is planned for 2015.

Mosquitoes that vaccinate against malaria

What if insects were used as an inexpensive way to vaccinate populations?

This idea was tested in 2010 by Shigeto Yoshida’s team at Jichi Medical University in Shimotsuke, north of Tokyo.

One of the malaria-carrying mosquitoes, Anopheles stephensi, was genetically engineered to deliver a malaria vaccine in its saliva.

Mice that were bitten by the mosquito several times developed antibodies to the parasite.

In 2012, the Japanese team demonstrated the effectiveness of the method against another strain of malaria .

These “flying syringes” could someday provide an alternative to traditional treatments, even if the forceful vaccination of an entire population will raises serious ethical questions.

GM insects against malaria

The British company Oxitec is also working on a transgenic mosquito to combat malaria.

The stakes on this are high, but the challenge is higher still, because the disease is transmitted not by one, but by dozens of different mosquito species.

“I don’t think that this technique will work against malaria,” says Paul Reiter from the Pasteur Institute in Paris. “The disease is too complex.”

It has an unglamorous name – OX513A – but a decidedly important mission: to reduce, and hopefully eliminate, populations of Aedes aegypti, the principal mosquito vector of the dengue virus. With Brazil’s decision in April 2014 to allow the widespread deployment of this transgenic mosquito created by the British start-up Oxitec, OX513A will become the first genetically modified creature to be released into the wild.

Dengue fever is rampant in tropical and subtropical regions; 50-100 million people are infected every year, of whom 25,000 die, according to the World Health Organisation. In the absence of any treatment or vaccine, the number of cases has risen steadily for the past 50 years.

The disease is transmitted mainly through the bite of the female A. aegypti mosquito. The Asian tiger mosquito A. albopictus also transmits the disease, though less effectively; it is responsible for a few observed cases in Southern France.

Standard techniques to combat A. aegypti – from preventive measures (eliminating breeding areas) to chemical assaults (spraying insecticides) – have not proven effective. As a result, the new approach has garnered considerable interest.

“Brazil recognised the intrinsic safety of our mosquitoes and the negligible risks to the environment,” says Hadyn Parry, Oxitec’s director. Still, the authorisation received from Brazil’s National Technical Commission for Biosecurity is just the first step. “Now we need to receive a commercial permit from the Minister of Agriculture, which normally takes six to nine months.”

Sterilising insects, revisited

Oxitec’s strategy is similar to the familiar technique by which male insects are irradiated to render them sterile and then released in large numbers. As a result, the majority of eggs laid by females are non-viable. The strategy was used successfully in the U.S. against Cochliomyia hominivorax, nicknamed the screw-worm fly for the way its maggots burrow into and devour the tissue of livestock.

Instead of irradiating males, Oxitec’s transgenic method consists of introducing two new genes into the male A. aegypti. One of them codes for a killer protein and the other for a fluorescent marker that allows researchers to monitor and track the transgenic population. A critical aspect of the system is an antidote: the antibiotic tetracycline deactivates the lethal protein, enabling OX513A to be bred in the laboratory.

The genetically modified mosquitoes are released into the wild in numbers large enough to outnumber wild males. Without the antibiotic, the offspring would die before attaining maturity, as do the transgenic males.

Several field trials of OX513A conducted since 2009 in the Cayman Islands, Malaysia and Brazil have demonstrated the technique’s effectiveness in reducing A. aegypti populations by 80-90 per cent after six months.

“Every two weeks we released on average 10-15 transgenic mosquitoes for every wild male,” explains Parry. “After six months, the frequency and number of releases can be reduced, but they need to be maintained over the long term.”

“It’s a fantastic technique,” says Ilona Kryspin Sørensen, research director at the Technical University of Denmark and member of the GMO working group at the European Food Safety Agency. “It is less difficult than sterilisation by irradiation, less dangerous than insecticides and has no effect on other animals.”

Even so, the technique is costly. Jayme Souza-Neto, a scientist at São Paulo State University, estimates the cost for a city of 50,000 inhabitants at $900,000 to $2.2 million the first year, and $450,000 per year after that.

An unproven technique

Just how effective the method will be in reducing the transmission of dengue fever remains unclear. “It’s conceivable that another species of mosquito, such as A. albopictus for example, could replace the one eliminated by Oxitec as a vector,” notes Christophe Boëte, a researcher at the Institute of Research for Development (IRD) in Marseille.

Scientists also worry that the new mosquito could develop resistance to the lethal gene or come into contact with antibiotics used in agriculture that could counteract the effect of the killer gene. Paul Reiter, from the Laboratory of Insects and Infectious Diseases at the Pasteur Institute in Paris is confident. “We know that OX513A eventually die and that the killer gene cannot be transferred to another species.”

Another fear is that some female transgenic mosquitoes could accidentally be released with the males, which would end up increasing the population of disease vectors because it is the females that transmit the disease. GeneWatch UK warns that the partial or temporary reduction in mosquito populations could actually lead to a resurgence of a more virulent form of dengue fever. But this argument also applies to non-genetic techniques of combating dengue fever by reducing mosquito populations.

Insufficient risk analysis

The first release of “kamikaze” mosquitoes in 2009 was controversial. “Oxitec was very secretive about the trials on Grand Cayman,” says IRD’s Boëte. “There should have been consultation with the scientific community concerning the legal, ethical and societal issues related to these experiments.”

Helen Wallace, head of GeneWatch UK, adds: “Under the Cartagena Protocol on Biosafety, Oxitec should publish a risk assessment based on criteria defined by the European Union; it has not done this.” She also points out that Oxitec has not published the results of its trials in Brazil.

The company has begun another trial in Panama and hopes to initiate one in Florida by the end of the year, though this one will require a green light from the U.S. Food and Drug Administration.

A world map showing the presence of dengue

Presence of dengue in the world. The disease infects 50 to 100 million. (Source: Centers for Disease Control and Prevention.)

By Sabine Casalonga

Technologist 02.004

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