Florida v. GM mosquitoes

British biotech Oxitec believes its genetically engineered insects will slow the spread of dengue fever, but Key West residents don’t want the mutant mosquitoes in their backyards.

“It may sound like the premise of a science fiction novel,” wrote Florida mom Mila de Mier in an email urging her fellow citizens to sign a petition to prevent the release of “mutant mosquitoes” – insects that have been genetically modified to combat the disease dengue fever – in her Key West neighborhood. To me it sounds more reminiscent of a science fiction film, specifically the 2000 release X-Men. Early on in the movie, we see fictional senator Robert Kelly speaking to the worried masses about the “mutant problem” and demanding that any such individuals to be officially registered to ensure public safety. Our real world mutants, genetically modified organisms (GMOs), inspire similar panic. Debates over GMOs often contain more rhetoric than science, and it can be difficult to separate useful information from emotional overreaction. Supporters of GM mosquitoes believe they can save lives. But will these insects work toward the common good, like Professor Xavier’s X-Men? Or will they go the Magneto route of chaos and destruction?

The disease

Dengue fever is caused by a virus whose principle vector in the western hemisphere is the Aedes aegypti species of mosquito (Aedes albopictus mosquitoes can also transmit the virus.) A mosquito that drinks the blood of a human infected with dengue can acquire the virus and (after a 8-12 day incubation period) can spread it to any other person it bites for the duration of its life (days to weeks, by that point.)

In humans, the disease manifests with symptoms such as high fever, severe headache and pain behind the eyes, pain in muscles, joints, and bones (it’s also known as break bone fever) rash, and “mild” bleeding (you know, just from the nose or gums, no big deal…) Some people get milder symptoms, but a portion of victims acquire a more severe form of the disease called dengue hemorrhagic fever (DHF) which can include leaking from the capillaries (your smallest blood vessels) and thus circulatory failure and death. Prompt medical treatment can improve patient outcomes, but it consists mostly of supportive therapies like fluid replacement. There is currently no vaccine or antiviral medication for dengue fever.

The other dengue spreader – A. Albopictus. Image Credit: James-Gathany/CDC.

Dengue fever is an emerging disease. Prior to WWII, Aedes mosquitoes were found mostly in Africa and Southeast Asia, but they’ve since made their homes around the world, including in the Americas. Dengue is now endemic in over 100 countries and, according to the World Health Organization, causes 50 to 100 million infections yearly, with half a million of these being the more severe DHF form. About 2.5 percent of cases (mostly in children) result in death.

Aedes mosquitoes are found in the southern United States as well. But while the disease is common in northern Mexico and the Caribbean, states like Texas and Florida have largely been spared from outbreaks of the virus. This is certainly not for a lack of mosquitoes in those states. Rather, U.S. citizens, who tend to live in screened, air-conditioned homes, don’t have as much contact with mosquitoes as those living in poorer nations.

Nevertheless, the disease does crop up from time to time. In 2009, 27 cases of dengue were found to have originated in Key West, Florida. The outbreak continued into 2010 producing an additional 63 cases. A total of 90 may not seem like much, but Florida officials were not eager to see another round of the potentially lethal disease. They’ve been dutifully dumping pesticides into the area to control mosquito populations, and recently they began exploring the option of deploying genetically modified mosquitoes.

The cure?

While many people react to GMOs with anxiety, too few take the time to understand the science behind these novel organisms. So before discussing pros and cons of fighting dengue with GM mosquitoes, let’s at least get a rough idea of how they’re designed.

The mosquitoes at the center of Florida’s controversy are made by Oxitec, a British biotechnology company started from the zoology department at the University of Oxford. While some genetic engineering has focused on creating insects that cannot spread disease, Oxitec’s aim is to prevent dengue by reducing the population of the mosquito species that carries it. The concept grew out of the sterile insect technique (SIT), which uses radiation to sterilize male insects in the lab and then releases them en masse into the wild to fruitlessly mate with females. Females that mate with the irradiated duds produce no offspring, so if sufficient numbers of sterilized males are released the overall population declines.

Unfortunately SIT doesn’t work well with mosquitoes. Heartier insects like the Medfly and (gross) the screw-worm can take a dose of radiation and still attract mates. But mosquitoes are delicate things. Irradiation renders them too weak to win mates in the wild. Even in large numbers they just can’t compete with the local skeeters.

To reap the benefits of SIT without the crippling radiation, Oxitec scientists use a technique called RIDL – Release of Insects containing a Dominant Lethal gene. Dominant because only one copy of the gene (from the lab-reared males) is needed, and lethal because it kills insects carrying it and also kills their progeny before they can reach adulthood. You might be asking, “How is a dead mosquito supposed to produce offspring?” Well, it turns out there’s an antidote to the killer gene. When the gene is inserted into insects it results in overproduction of a protein called tTA and disruption of normal cell function, leading to death. But when the insects are given tetracycline – an antibiotic that works by inhibiting protein synthesis – the destructive gene is suppressed and life goes on. Take away the tetracycline and the bugs’ days are numbered (even by insect standards.)

OX513A, the genetically modified Aedes aegypti mosquito Key West residents are trying to keep out of their neighborhoods, is an RIDL creation. Raised in the lab on a diet supplemented with tetracycline the insects are protected from their lethal genes. But once released into the wild and deprived of their meds, they’ve got just enough time to mate and die. And any offspring sired by these doomed insects are designed to expire by the late larva or pupa stage.

Oxitec stresses that the protein produced by the lethal gene isn’t a toxin, so it won’t harm any animals that happen to eat the lab-made insects. Additionally, since only female mosquitoes bite, and almost exclusively males are released (separation of sex is done by size at the pupal stage, resulting in only 1 to 0.1 percent females in the released batches) there’s extremely little chance of GM mosquitoes biting humans.

The people at Oxitec seem to have thought of everything. But then so did the scientists in Jurassic Park, and that led to several hours and two sequels worth of “unintended consequences”. So maybe we should consider some of the objections to GM mosquitoes.

The controversy

I’m not going to focus much on concerns fueled by fear of the unknown. The belief the all things GMO are dangerous follies of scientists bent on “playing God” ignores how much tampering with nature we do already. Agriculture has long been an experiment in genetic modification. The corn and chickens we use as food, even those labeled “organic”, have little in common with their wild counterparts. Years of breeding have given them their present form. This is not to say that everything that can be done should be done, or that all our innovations have been positive ones. But new technologies should be evaluated by weighing their risks and benefits rather than solely on the merits of how close they are to “natural”.

With or without DDT. So many alternatives back in the day. Image Credit: Kevin Krejci.

One such consideration is what effect OX513A might have on the environment. For instance, would wiping out Aedes aegypti (or drastically reducing their numbers) deprive other animals of food? While these mosquitoes don’t live in a vacuum, they’re also not an indigenous species in Florida (or Brazil, where they’re being released in a larger trial). They’re invasive newcomers, and no animal relies on them exclusively for its sustenance. Furthermore, the pesticides Florida is currently using to control mosquitoes have the same goal (that is, killing the little jerks), so depleting the Aedes aegypti population is obviously a risk we’re okay with. In theory, RIDL  technology should be a more eco-friendly approach than traditional insecticides – it targets a single species, and it doesn’t introduce chemicals into the ecosystem. But then we’re sort of used to chemicals, whereas GMOs are still new and scary.

Also a bit worrisome is the mostly male release and the observation that, well, not every offspring with the lethal gene completes it mission of dying before adulthood. When OX513A males were mated in the lab with Cayman Island wild females (prior to field testing in the area) the mortality rate was actually 96.5 percent. That’s actually quite good (the estimate is that anything over 90% will do in terms of population reduction) but 100 percent would certainly be preferable. So there will be some biting female out there. Not a lot, but some.* And while the scientists assure us that the pivotal protein intended to kill these mosquitoes is neither toxic nor present in their saliva (that’s what the females inject into your skin when they bite) it would be reassuring to see some experimental data demonstrating that a bite from one of these bugs would result in no more than the standard itchy welt.

Critics also remind us that Oxitec isn’t a non-profit group, it’s a company with a product to sell. This can easily be seen on their website, which features spiffy pull-down menus of their various models in both agricultural and health related realms. I’m thinking of purchasing a box of Aedes aegypti OX3604C (the exciting flightless female phenotype) and releasing it into my mosquito-beleaguered lawn. (Kidding, kidding, I’m pretty sure I’m not legally allowed to do that.) And Oxitec hasn’t helped its image by being less than forthcoming about its products and field trials. For instance, they’ve sometimes referred to their mosquitoes as “sterile” rather than explaining the genetic technique employed. Given public apprehension about genetic modification, it’s not surprising the company would be tempted to gloss over details, but it’s a terrible approach. It’s like saying to your boss or spouse or whoever, “I had to lie to you, because I knew you’d freak out if I told the truth.” Careful explanation (though it can still fail) offers a better chance at preventing GMO terror than omitting information and denying any possibility of risk.

Or we can just buy one of these for every man woman and child in Key West. Image Credit: Robert Couse-Baker.

But Oxitec isn’t the only party straining to make their angle sound convincing. In her email Mila de Mier goes on to write, “But it’s been years since we’ve had a case of Dengue Fever in Key West, because we have prevention systems in place. Oxitec — a British corporation — thinks its mutant mosquitoes would be a cheaper solution…” Just to be clear, “years” = about 2 years and “prevention systems” = chemical insecticides. And while she paints Oxitec’s “cheaper solution” as a negative (as if cheaper is always inferior) for many countries struggling with dengue, resources are scarce. A cheaper technology is a more available technology.

Personally, my biggest concern is that these mosquitoes simply won’t work, or won’t work for long. Initial trials have been promising (a field trial in Brazil reported an 85% population reduction of A. aegypti in just one year) but it remains to be seen if these improvements can be maintained. In the Cayman Islands field trial, OX513A males managed to mate with wild females, but not as successfully as the wild males. To some extent, this can be remedied by releasing the laboratory males in larger quantities, so that they outnumber the locals. But one can’t help wondering if females who prefer the wild males to the mutants (and thus are more likely to have offspring) will eventually form the majority, thus creating a sort of immunity similar to what we see with insecticides. It would be great if RIDL technology could rid the world of pests and the diseases they carry, but it seems more likely that it will just keep them at bay until the next clever idea emerges.

*Anyone more experienced in statistics than I is welcome to work out the odds of being bitten by an OX513A mosquito, but I suspect it’s rather low.

Alex Reshanov

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