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 Aedes aegypti.
Aedes aegypti.

When we think of deadly creatures, we tend to think of fierce animals like tigers, grizzly bears, sharks, alligators and snakes. But these animals don’t kill about one million people a year. Mosquitoes do, according to the World Health Organisation.

Actually, the mosquitoes themselves aren’t lethal. They make buzzing noises when they fly near you and they cause your skin to itch when they bite you but at most that makes them an irritant or a nuisance. What makes them deadly are the viruses that they can carry and transmit.

In Malaysia, we’re all too familiar with dengue fever. Each of us probably knows people who have gotten it before. Some of us might have even gotten it ourselves. It’s that common. According to the Centre for Disease Control and Prevention (in the USA), approximately 100 million people each year suffer from dengue.

Not everybody dies from dengue fever but there’s no vaccine or real cure for it. You have to sit it out and hope that you survive. Some don’t. Every year, there are some unfortunate victims who die of it. But dengue is by far not the only deadly mosquito-borne disease. There’s also Zika fever, Zika fever, yellow fever, chikungunya and West Nile virus.

We ward off mosquitoes with mosquito coils and all kinds of insect repellents. But those are temporary solutions. How nice it’d be if we could eradicate mosquitoes all together. One strategy some scientists are trying is releasing genetically-modified mosquitoes that carry a lethal gene.


 Genetically Modified Mosquitoes (Oxitec).
Genetically Modified Mosquitoes (Oxitec).

Oxitec, a leader in this field, has developed genetically-modified mosquitoes known as OC513A (Aedes aegypti). To create this mosquito, Oxitec took a lab-grown strain originally from Cuba and mixed it with a strain from Mexico.

The male mosquitoes have what the company calls a “self-limiting” gene, which means that when they mate with a female, their offspring are not supposed to survive into adulthood (and thus not able to breed). In theory, this should kill off or at least drastically reduce the mosquito population.

This is how the company describes the self-limiting gene: “The self-limiting gene is at the heart of our method of insect control. When our male insects are released and reproduce with wild females, all of their offspring inherit a copy of this gene. The self-limiting gene disrupts the proper functioning of the insects’ cells by over-producing a protein in them, interfering with the cells’ ability to produce other essential proteins needed for development. So, by disrupting the insect’s normal development, the gene prevents it from surviving to adulthood.”

Oxitec’s genetically-modified mosquitoes are also equipped with a fluorescent protein gene, allowing for the easy identification of any offspring, which the company said at most would be about 3 per cent.

Like the self-limiting gene, it’s inherited by all offspring. This protein is found throughout the body of the larvae, pupae and adults, and glows red under a special light. As a result, with the right equipment you can easily tell genetically-modified mosquitoes apart from wild ones. By examining larvae from the field, researchers can see how many are offspring of genetically-modified mosquitoes and how many are wild ones.

The company has done a major trial in Jacobina, Brazil, where it released nearly half a million transgenic mosquitoes into the wild. Starting in 2013, and for a period of 27 consecutive months after that, Oxitec released 450,000 of these genetically-modified males.

The idea was to reduce the mosquito population in the area and it was initially successful, reducing the mosquito population in that area by a whopping 90 per cent. However, traces of the mutated insects have been detected in the natural population of mosquitoes, according to new research recently published by Scientific Reports. This has resulted in alarmist headlines in media all over the world.

A study led by a Yale University researcher has confirmed that some of the offspring of the genetically-mosquitoes didn’t succumb to the self-limiting lethal gene after all and not only survived to adulthood but also successfully bred with the local mosquitoes.

The research team, led by Yale University’s evolutionary biologist Jeffrey Powell, discovered that genetic material from OX513A did in fact trickle into the local mosquito population.

“The claim was that genes from the release strain would not get into the general population because offspring would die,” Powell, the senior author of the new study, said in a press release. “That obviously wasn’t what happened.”

Actually, the fact that a small percentage of the offspring would survive into adulthood was expected. Lab tests conducted by Oxitec prior to the Brazilian trials suggested that around 3 per cent of the offspring would survive into adulthood. But it was thought that they’d be too weak – effective infertile – and unable to reproduce. Some obviously did manage to do so.

The study said the researchers uncovered “clear evidence” showing that portions of the genome from the transgenic strain had “incorporated into the target population.” Depending on the samples studied, the researchers found anywhere from 10 per cent to 60 per cent of mosquitoes analysed featured genomes tainted by OX513A.

Crucially, the genetic material from OX513A that can be found in the native species has not been found to pose any known health risks to the residents of Jacobina. Powell and his team tested the hybrid mosquitoes to determine their susceptibility to infection by Zika and dengue and found “no significant differences.”

However, Powell argues that it’s the unanticipated outcome (of the males maturing into adulthood and successfully breeding) that should be of concern. “When people develop transgenic lines or anything to release, almost all of their information comes from laboratory studies. Things don’t always work out the way you expect,” he said.

In nature, the intermingling of traits between different species can sometimes result in a more robust new strain. This is a phenomenon known as “hybrid vigour.” The study speculated that the intermingling of genetic traits might have also introduced entirely new characteristics, such as increased resistance to insecticides.


 Fluorescent Marker (Oxitec).
Fluorescent Marker (Oxitec).

This speculation has resulted in a strong pushback from Oxitec. “We’re not surprised by the results, but what we’re surprised by are the speculations that the authors have made,” said Nathan Rose, head of scientific and regulatory affairs at Oxitec.

He added that the company has asked Nature Research, which publishes Scientific Reports, to “address the range of misleading and speculative statements” in the study. Scientific Reports on September 17 published the following editor’s note: Readers are alerted that the conclusions of this paper are subject to criticisms that are being considered by editors. A further editorial response will follow the resolution of these issues.

Interestingly, it’s not just Oxitec which has complained about the study. There’s also backlash from some of the researchers themselves. Six out of the 10 researchers involved in the study are reportedly calling for the retraction of their study.

One co-author, Margareth Capurro a molecular biologist at University of Sao Paulo, told the magazine that the final version of the study didn’t match the data that she and her collaborators submitted to their co-authors. She also said that the published text was different from the manuscript that all the authors had agreed upon. Her lawyer has said that Capurro “does not support the inflammatory, dramatic, and speculative statements contained in the manuscript.”

Obviously some clarification needs to be made and perhaps further research needs to be done to determine the safety of such a programme. It would be a shame if such a novel and effective approach like Oxitec’s is rejected by the masses because of alarmist headlines about genetically-modified mosquitoes, which ultimately end up being unfounded.

Oon Yeoh is a consultant with experiences in print, online and mobile media. Reach him at [email protected].

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