Mosquitoes, and the diseases they carry, have been a threat to human health for millennia. Despite advances in research and efforts in disease control, mosquito-borne illnesses such as malaria and dengue fever still ravage much of the developing world, hindering efforts to raise the global standard of living. On November 11th, 2010, Oxitec, a biotech company based in Oxford, UK, announced that they had completed the first field trial to reduce mosquito populations using genetically modified Aedes aegypti mosquitoes. The declaration that the trial was a success has been met with mixed reactions, including fear of genetically modified organisms, concerns about ecosystem stability, and doubts that the strategy is feasible for controlling the spread of disease [1].

The Aedes aegypti mosquito is the primary carrier of dengue fever and yellow fever, among other tropical infectious diseases. The World Health Organization estimates that 50 million people every year are infected by dengue fever alone, with 2.5 billion more at risk. The dengue virus causes fever, joint pain, and hemorrhagic bleeding, symptoms that can lead to death, and effective vaccines have proven difficult to develop due to the multiple strains of the virus. Traditional malaria prevention methods, such as mosquito nets, are less effective in controlling the spread of dengue because Aedes aegypti also bite during the day. The most promising method for disease prevention is through a reduction in the mosquito population [2].

A new method for disease prevention

The strategy employed by Oxitec is termed “Release of Insects carrying a Dominant Lethal” or RIDL technology. This strategy relies on the release of male mosquitoes engineered to contain a gene which, when passed on in mating, render the female’s offspring inviable. Since male mosquitoes don’t bite (females need the extra nutrients in blood to produce eggs), massive numbers of modified male mosquitoes can be safely released into the environment. The modified mosquitoes can be raised in the laboratory environment because a food additive suppresses the lethal gene. By sheer number, modified males are more likely to mate with females than the native males, causing the mosquito population to fall. Working with local government agencies, Oxitec released 3 million male mosquitoes (an estimated 10 males for every native female) within a 40-acre area on the Grand Cayman island. They found that the mosquito population dropped 80% in this area compared to regions on the island where mosquitoes were not released. While the area tested was too small to noticeably lower local dengue cases, mathematical models predict that an 80% mosquito population reduction over the entire island would significantly reduce infection [1,2].

In evaluating the safety and efficacy of this mosquito introduction, it is useful to remember that RIDL is not a new idea, but rather an extension and improvement of an earlier approach called sterile insect technique (SIT). In the 1920’s, scientists discovered that exposing male insects to gamma radiation rendered them infertile. In the 1950’s, the large-scale release of infertile screw-worm flies eradicated this pest in the United States and Central America. Millions of infertile screw-worms are still being released each year in Panama to prevent their spread further north.  Although it has proven to be an effective strategy for the control of certain agricultural and human diseases, in recent years, concerns have been raised over the security of sources of gamma radiation, which are necessary for traditional SIT. Since RIDL renders the mosquitoes sterile through the controlled introduction of a new gene, radiation is not necessary [3].

Is it a threat to the environment?

The main opponents of using these modified male insects to control population are divided into two camps: those who are concerned that decimation of the insect in question will lead to ecological collapse, and those who doubt the ability of this strategy to effectively reduce the insect population of large areas. The answers to both of these concerns can be approached by examining the past record of radiation-based SIT.

The environmental impact of releasing organisms that are designed to reduce the species population is a legitimate concern that should be evaluated carefully. The genetic mutation of the mosquitoes themselves is not dangerous to people, and since the mutation prevents the animal from producing viable offspring, there is also no danger of it spreading into the natural population [1]. As a result, the number of genetically modified mosquitoes in the environment can be carefully controlled by the number that are released, since the genetically modified population can only decline and not increase by natural means.

A drop in mosquito numbers, while the goal of the project, may itself be detrimental to the environment, since mosquitoes serve roles as both pollinators and food within an ecosystem. However, there are 3500 different species of mosquitoes, and RIDL allows the targeting and reduction of a specific disease-carrying species, while leaving other species of mosquitoes unaffected, as opposed to pesticide application or swamp draining. In addition, the variety and complexity of the insect world make it likely that if one species decreases in number, its role in the ecosystem can be filled by another insect species [4]. Fears of ecological collapse should also be tempered by the fact that past efforts to eradicate species using SIT have shown that maintaining a pest-free area is an ongoing battle, necessitating the introduction of new sterile males every year to prevent re-invasion of the area [3]. Careful monitoring of the environmental impact of any species reduction, and taking immediate action to reduce the number of modified mosquitoes released if any ill effects are seen, can help ensure that the ecosystem is not negatively impacted.

Future potential for a budding technology

In some ways the more serious concern, especially given past campaigns using SIT, is whether RIDL will work in large areas. Islands, such as the Cayman Islands where Oxitec began trials, are promising first targets to employ this strategy, since the area is limited and the borders are clearly defined. However, as seen with the eradication of the screw-worm from North America, sterile insects must be continually released to create a “buffer zone” and prevent repopulation. Therefore, this strategy may be difficult to implement in large landmasses without clear geographical boundaries, such as Africa. Several countries in Africa are currently attempting to employ the SIT method to eradicate the tsetse fly, which is responsible for the spread of sleeping sickness, but efforts are hampered by high costs and the difficulty of minimizing the constant risk of reinvasion from surrounding infected countries that are not implementing the same strategy. Despite the high costs, many countries are still willing to embrace RIDL or SIT, saying that the economic costs of the disease are higher still. In order for the strategy to be maximally effective, a coordinated region-wide or even continent-wide effort will need to be made. Global aid and health organization support would likely be necessary for the strategy to successfully reduce disease in these areas [3].

For better or for worse, introducing genetically modified mosquitoes is unlikely to completely wipe out the mosquito population in an area. However, it does show promise as a technique to help reduce mosquito populations, especially in geographically isolated environments. Compared to traditional methods of mosquito eradication, the effects of RIDL are much more specific and could possibly lead to smaller environmental impacts. Further work is necessary to establish the effectiveness RIDL and to adapt this technique for the unique geographical considerations in affected areas. Considering, however, the heavy toll of mosquito-borne diseases around the world, this technology is a method that deserves serious evaluation and consideration.

Rebecca Reh is a graduate student at Harvard Medical School

References

1) Martin Enserink, “GM Mosquito Trial Alarms Opponents, Strains Ties in Gates-Funded Project”. Science – News of the week 11/19/2010.

2) London (AP) “Mutant mosquitoes fight dengue in Cayman Islands”. Associated Press, 11/11/2010. http://www.google.com/hostednews/ap/article/ALeqM5iJg3GFfMS2oAMzerUoes59s_o6ZQ?docId=e53509adbb294717a33deb7a1ae3e9dd

3) Martin Enserink, “Proven Technology May Get a Makeover”. Science – News Focus 7/20/2010.

4) Janet Fang, “A world without mosquitoes”. Nature – News Feature 7/22/2010. http://www.nature.com/news/2010/100721/full/466432a.html

Links of Interest

Oxitec Television and Radio page with video clips covering the RIDL technology and use: http://www.oxitec.com/our-news/television-and-radio/

Progress and prospects for the use of genetically modified mosquitoes to inhibit disease transmission. Report on planning meeting 1; World Health Organization, Geneva, Switzerland, 4-6 May 2009 http://apps.who.int/tdr/publications/training-guideline-publications/gmm-report/pdf/gmm-report.pdf

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