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September 15, 2014 | By:  Julia Paoli
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Genetically Modified Mosquitoes Pave the Way for Dengue Fever Prevention

Over 40% of the world's population is at risk of contracting Dengue Fever - that's more than 2.5 billion people. Although less well known than other maladies, Dengue Fever is a serious global threat and may become even more widespread in the coming years. Dengue Fever is caused by any one of four related viruses which are transmitted to humans by mosquitoes. Scientists in Brazil are using genetically modified mosquitoes to combat Dengue Fever's spread.

The Aedes aegypti is the primary mosquito responsible for the 50 - 100 million infections each year according to WHO. Humans become infected through the bites of only the female mosquitoes. Once infected, a person experiences a severe, flu-like illness. Symptoms include high fever, muscle and joint aches, severe headache, nausea, vomiting and rash - just to name a few. In some patients severe Dengue Fever (a.k.a. Dengue Hemorrhagic Fever) can form. Symptoms include severe abdominal pain, persistent vomiting, shock, leaky capillaries, and circulatory system failure. With prompt medical care mortality from DHF can be reduced from 20% to less than 1%.

There is no vaccine or medicine capable of preventing or curing Dengue Fever and DHF. The most effective preventive measures are those that "avoid mosquito bites", says the CDC. But fear not! Scientists in Brazil are releasing genetically altered Aedes aegypti mosquitoes based on research conducted at the University of California Irvine and by the English company Oxitec.

In the past, pest populations could be reduced using the Sterile Insect Technique (SIT). This method calls for male insects to be sterilized by exposing them to radiation. A sterilized male can still produce sperm and fertilize female's eggs but the resulting offspring have only a very short life span. The sterile males are released into the wild. Female mosquitoes generally mate once in their lifetime so if a female mates with a sterile partner then she will not produce healthy offspring. Over time, the pest population is reduced. Unfortunately, male mosquitoes are not very sturdy. The exposure to radiation makes them very sickly and weak. As a result, female mosquitoes in the wild are not inclined to mate with sickly males.

With the help of the University of California Irvine, Oxitec has created a way to reduce mosquito populations without using harmful radiation. The secret to Oxitec's success lies in the world of genetics. Scientists added an extra gene to the mosquito's DNA which releases a protein that hinders a cell's ability to function. The protein produced, tTA, functions as a "switch that controls the activity of other genes." Protein tTA can also communicate with other proteins which are pertinent to controlling cellular activity, and therefore stop cells from activating genes necessary for survival. What does this mean for genetically modified mosquitoes? The extra gene makes them very sick and causes them to die before adulthood.

Some may wonder how male mosquitoes can live long enough to be released into the wild and mate if the extra gene is so lethal. Whenexposed to the drug tetracycline the tTA protein stops working. While in the lab, the modified mosquitoes are fed tetracycline to stay healthy. In the wild, modified males who mate pass on the deadly gene to their offspring. Due to a lack of tetracycline in the wild, offspring of the modified males die from the gene since they are not being fed tetracycline. A decrease in the amount of offspring who survive into adulthood causes the mosquito population to decline and therefore lessens the threat of contracting Dengue Fever.

Inserting new genes into a mosquito's DNA is not an easy task. The process starts with the mosquito eggs, which are 1 mm long tubes (.039 of an inch long). Scientists inject a miniscule amount of new DNA containing the lethal gene, about 10 thousand-millionths of a litre, into the mosquito eggs using a special glass needle. The needle is so sharp that its point can only be seen under a high-powered microscope! Not all the injections are successful. In a batch of one thousand injected mosquito eggs only one may actually incorporate the new DNA into its genome. Some of the eggs will not survive while in others the injected DNA will not be incorporated into the genome. In only a few eggs will the new DNA become incorporated into the mosquito's genome. After the eggs are hatched, the young mosquitoes are monitored until adulthood and mated with other mosquitoes. If the new DNA has entered sperm or egg cells then the lethal gene can be passed on to offspring.

What I find really exciting is that in addition to the lethal gene, scientists also inject the mosquitoes with a fluorescent gene (they glow!!). The fluorescent gene allows researchers to quickly identify which mosquitoes are modified.

In Brazil, initial results regarding the release of the modified mosquitoes appear positive. In the Itaberaba neighborhood in the Bahia region of Brazil, millions of the genetically modified male mosquitoes were brought in. An impressive 84% of the mosquito larvae now carry the gene. The Brazilian government has approved the release of the altered mosquitoes in five more neighborhoods. Additionally, in the Cayman Islands and Malaysia the modified mosquitoes have been released without any unfavorable outcomes.

Despite the success so far with the altered mosquitoes there are some deterrents. Some people do not trust genetically modified organisms and are worried that modifying an insect's DNA might accidentally create a superbug. A superbug may cause environmental and agricultural havoc. In my opinion, the Dengue Fever situation will probably only get worse over time. We might as well give the modified mosquitoes a shot.


References:

Campbell, C. "If You're Not Worried About Dengue Fever, Here's Why You Should Be." Time. November 18, 2013.

CDC. Dengue (2013).

Oxitec. "Using genes to control insects: the Oxitec solution." Oxitec. 2013.

Oxitec. "More on the science: how does oxitec make genetically modified mosquitoes?" Oxitec. 2013.

Mahr, K. "Genetically Modified Mosquitoes Released in Malaysian Forest." Time. January 28, 2011.

Sifferlin, A. "How Mutant Mosquitoes Are Fighting Dengue Fever." Time. November 9, 2012.

The New York Times. "Dengue Hemorrhagic Fever." The New York Times. 2013.

WHO. Dengue and severe Dengue (2013).

Images:

http://en.wikipedia.org/wiki/File:Aedes_aegypti.jpg




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