With all the recent media coverage about the Zika virus epidemic, it is surprisingly difficult to find a source that answers basic questions about the science surrounding the news. Thankfully, the folks at Osmosis.org have created an excellent educational video that lays out the basic need-to-know information on Zika and the recent outbreak.
Zika virus has been around, and widely ignored, for over 60 years. In adults, a Zika infection can result in symptoms not much worse that the common cold, and 4 out of 5 infected adults have no symptoms at all. Then suddenly in 2015, cases of microcephaly in Brazil jumped from less than 200 to over 4,000 per year. Babies born with congenital microcephaly have an abnormally small brain and skull and can suffer cognitive and motor function impairment. Epidemiologists in Brazil noticed that the increase in microcephaly cases corresponded with a Zika virus outbreak in the region, and since then there has been a global push to control or eradicate the virus.
It is important to pause here for a minute to point out that no direct link between Zika and microcephaly has been proven. Zika has been found in the brain tissue of several newborns with microcephaly who died shortly after birth, but this does not constitute proof that Zika was the cause of the microcephaly. The World Health Organization acknowledges this, but states that the link is “strongly suspected.” Assuming that Zika is the culprit, what can we do about it? No treatment or vaccine exists against Zika, and such measures can take years to develop. Several groups have decided instead to go after the Zika virus by targeting its vector, the Aedes mosquito.
Zika is an arbovirus (arthropod borne virus) that is transmitted by two species of mosquito in the genus Aedes. People infected with Zika can pass the virus back to mosquitoes that bite them, infected mosquitoes bite other humans, and so the virus is spread. Brazil is spraying pesticides and going door to door looking for mosquito breeding grounds, but a little standing water is all that Aedes needs to breed, and there is no shortage of that in Brazil. A few enterprising scientists think they have a better way: by harnessing the power of genetic engineering, they will infiltrate the Aedes population from the inside and destroy it.
A company called Oxitech (Oxford Insect Technologies) is doing this now. Their product, a genetically modified Aedes mosquito unaffectionately termed OX513A, is currently being released by the thousands at select field-test locations in Brazil. The OX513A mosquito is an Aedes mosquito with a couple of modifications. First, it glows for easy identification; and second, it is armed with a genetic time bomb. A construct inserted into the Aedes genome produces a synthetic protein called tTAV. tTAV in turn blocks transcriptional machinery inside each cell of the mosquito and keeps the cell from making proteins that it needs to survive. tTAV also acts as its own transcription factor, creating more of itself in a positive feedback loop. The result is that before long, each cell of the mosquito begins to die, resulting in the death of the mosquito itself.
The OX513A mosquitoes being released are all male, and this is key to the process. First of all, male mosquitoes don’t feed on blood and cannot transmit disease. Secondly, after being released the male OX513As survive just long enough to mate with wild females, passing on the dominant lethal genetics to their offspring. Sufficient numbers of OX513A males outcompete wild males for mates, and progeny of these matings die before reaching adulthood. Over time, with enough males released, the entire population of Aedes could theoretically be wiped out.
A similar method has been used before. In the 1950’s Raymond Bushland and Edward Knipling developed the “sterile insect technique” to combat a parasitic fly called the screwworm. Screwworm flies lay eggs into cuts in the skin of warm-blooded mammals, and the hatched larva bore into living flesh. Screwworm larva can kill an infected cow within 10 days, and in the 50’s screwworm infestations caused millions of dollars of damage to livestock each year. Bushland and Knipling used radiation to sterilize and release masses of male screwworm flies into infested areas around the continent. By the 1980’s screwworms were eliminated north of the Panama canal. This massive success earned Bushland and Knipling the 1992 World Food Prize and has been called “the greatest entomological achievement of the 20th century.”
Now, using the precise tools of genetic modification, we are entering an age where eradication of entire species is becoming easier than ever. Along with the Aedes mosquito, Oxitech is developing genetically modified versions of major crop pests like the diamondback moth, pink bollworm, medfly, mexfly, and olive fly. The older technique using radiation has also been used to control populations of mediterranean fruit fly, melon fly, and tsetse fly. Controlling insect populations in this way is extremely targeted and effective; only the target species is directly hit as opposed to the huge off-target effects of spraying pesticides. In fact, a number of groups have blamed pesticides, and not Zika itself, for the microcephaly cases in Brazil. Before the current outbreak, the Aedes mosquito has been the target of mass pesticide initiatives because of other nasty diseases it transmits such as dengue, yellow fever, and West Nile virus.
Perhaps the thought of genetically modified insects flying around gives you the willies. Perhaps our attempts to control insects genetically could fail, or even have unintended, disastrous consequences. This author cannot help but recall a skeptical Jeff Goldblum in the film Jurassic Park who predicts, “life, uh, finds a way.” There is certainly an argument to be made for caution before messing around with genetics. The FDA lists two genetically engineered animals on their website: the AquaAdvantage Salmon, approved for human consumption last year; and the Oxitec mosquito. The mosquito is not yet approved for general use in the United States, but field trials are currently taking place in Florida.
Surely the thought of wiping out entire populations of insects will raise red-flags among environmentalists and ecologists as well. We know enough now to realize that we live in an interconnected web of species, and wiping out one can have devastating consequences on the delicate balance of that web. One point to remember here is that the Aedes is an invasive species. Native to Africa, it has now spread around the world, likely due to inadvertent human transport. We brought Aedes to Brazil in the first place; does that give us the right, or even the responsibility, to eradicate it now?
The truth of the matter is, mosquito borne diseases kill over 1 million people each year. And between 20% and 40% of potential world food production is currently lost to insect pests. We are in a war with disease bearing mosquitoes and crop pests whether we like it or not. Right now we are fighting this war with potentially dangerous and environmentally harmful pesticides. Could genetically modified insects present a solution to these problems? Or are the risks and potential consequences too great to justify this new approach? Choosing pro or con can be a vast oversimplification of such a complex topic. It is becoming increasingly important for each of us, from all walks of life and all sides of the argument, to wade through these complex issues together. As we enter the modern age of synthetic biology, education about these and other issues will form the basis of how we will come together as a society to influence the course of our global community.