News Mosquito wars The release of genetically modified (GM) mosquitoes into the environment to fight dengue fever is about to open a new front in the war against vector-borne diseases. Sarah Cumberland reports. Dengue fever is a disease that afflicts than 50 years by releasing laboratory- Oxitec/Nimmo an estimated 100 million people per reared insects made sterile through irra- year. There is no vaccine and no cure. diation. Native females that mate with The mosquito-borne viral infection the sterile males produce non-viable Two Aedes aegypti larvae are shown glowing red causes severe flu-like illness, often or green under a fluorescence microscope because offspring, leading to a decline in the they carry a gene encoding a fluorescent protein. requiring hospitalization, and can de- natural population. The governments velop into the potentially fatal dengue of Guatemala, Mexico and the United haemorrhagic fever. States of America (USA) irradiate some has also taken a lead in risk assessment Experts agree that the only suc- two billion male Mediterranean fruit of GM mosquitoes. The Academy of cessful way to control or prevent this flies every week, before releasing them Science in Malaysia has conducted an disease is to combat its vector. But into the wild to mate. Another agricul- independent review of these semi-field this task is extremely difficult as the tural pest, the parasitic screwworm, has trials and has recommended that the Aedes mosquito genus thrives in urban in this way been eradicated from the project proceed to the next step once it settings and bites during the day. Its USA and much of Central America. has passed regulatory and ethical clear- eggs can lie dormant in dried-up water ances. In December 2008, international receptacles, such as in car tyres, which experts took part in a meeting convened are often shipped around the world. by the United Nations Development Fortunately a new front is forming As scientists, we Programme (UNDP) at IMR to discuss in the battle against this tenacious are aware of the need risk assessment with Malaysian and mosquito as years of scientific work to take a cautious regional scientists and regulators. come to fruition. In the next year or approach. We want The next stage will be to con- two, if biosafety, regulatory and ethical to be as sure as we duct open-release trials in which the approvals and community consent mosquitoes are released into selected, are obtained, a new kind of mosquito can possibly be that naturally contained sites such as islands. could be released into the environment. the health benefit is According to Dr Yeya Touré, manager Created in the laboratories of Ox- unambiguous. of innovative vector control interven- ford University and Oxitec, a biotech- tions at the UNDP/World Bank/World nology company located in the south of Paul Eggleston Health Organization (WHO) Special England, these male mosquitoes of the Programme for Research and Training Aedes aegypti species will be on a mis- But this technique has not been in Tropical Diseases (TDR), these trials sion to mate, but not to breed. successfully used against mosquitoes may be just “a matter of months away”. They are in fact designed to cause because sterilizing doses of radiation “We are no longer talking about the wild females with whom they mate weaken them, reducing their ability to wild speculation,” says Alphey. “If the to produce offspring that die at the compete for mates, which is fundamen- pupa stage with the aim of signifi- funds are made available, I can see the tal to the method – until now. Luke cantly reducing the native population elimination of dengue from regions or Alphey, founder and research director below the numbers required to sustain groups of countries using GM technol- of Oxitec, working with colleagues dengue fever transmission. ogy integrated with other tools.” Good at Oxford University discovered that, Insect population suppression – news for the 2.5 billion people cur- employing what is known as sterile in- by inserting a single gene into the rently at risk of the disease. sect technique – has actually been used A aegypti’s DNA, it was possible to Since 1970, there has been a surge to control agricultural pests for more produce males whose offspring do not in dengue fever epidemics with more survive to adulthood. than 100 countries worldwide now Oxitec’s findings have now been seriously affected. Increased ship- successfully corroborated through the ping of goods and urbanization have world’s first semi-field trials held in been blamed for the introduction and collaboration with the Institute for spread of the Aedes mosquito into the Medical Research (IMR) in Malaysia. Americas and south-eastern Asia. These trials were held in a confined According to a study conducted field house that mimicked the natural by the Indian Institute of Management environment and aimed to test the GM in Ahmedabad, Aedes mosquito-borne Oxitec/Nimmo male’s mating competitiveness with disease – primarily dengue fever and unmodified insects. chikungunya, another viral disease, – A female mosquito of the Aedes genus, the main Malaysia, which has almost 50 000 costs India alone a hefty US$ 1.3 billion vector of dengue fever. reported cases of dengue fever per year, every year, 95% of that due to illness. Bull World Health Organ 2009;87:167–168 | doi:10.2471/BLT.09.020309 167 News But it’s not only the Aedes mos- quito and dengue control that are under the microscope. According to Paul Eggleston at Keele University in England, who has been working on developing GM mosquitoes since 1983, it is now possible to genetically modify all major taxonomic groups of mos- quito, including those of the Anopheles genus, which is the vector of malaria, and those of the Culex genus, the vector of lymphatic filariasis, which can lead to elephantiasis. The potential for a concerted pushback against mosquito- borne diseases is enormous. It is important to make the distinc- tion between population suppres- sion using a sterile insect technique – Oxitec’s approach – and another approach, known as population WHO/TDR replacement, which is under develop- ment. This more technically challeng- A health worker in Havana, Cuba, sprays insecticide in a tyre depot using a fogging machine. International trade ing strategy modifies the insect so that in tyres has spread the mosquito vectors of dengue fever around the globe. it can no longer transmit the parasite that causes dengue. It relies on GM insects mating with and permanently their governments to make informed consultation will bring together experts altering the genetic make-up of the decisions and weigh up the potential in global biotechnology, safety and wild population. benefits and risks. Scientists will also GM research, as well as regulatory and While prototypes of some of the be needed to implement the strategies, policy officials from WHO Member necessary components have performed to work in laboratories that will rear States. “The meeting will cover issues well in laboratory settings, population and distribute the GM mosquitoes in such as biosafety assessment, regula- replacement is several years away from their local settings. tory, ethics and the social aspects of field trial. “There are no plans to release research,” explains Touré. The techni- insects into the wild yet,” says Egg- cal consultation will be followed by leston. “As scientists, we are aware of the We are no a broader public consultation that need to take a cautious approach. We will be attended by nongovernmental want to be as sure as we can possibly be longer talking about organizations and advocacy groups, as that the health benefit is unambiguous.” wild speculation. If well as media representatives. TDR’s Touré concurs: “These the funds are made Despite all the buzz about GM [GM] mosquitoes have to replace the available, I can see mosquitoes, few believe they represent wild population,” he says. “We have to a silver bullet against mosquito-borne be sure that they are not going to in- the elimination diseases. Alphey himself sees GM as troduce any other issues through their of dengue from part of an overall disease management genetic modification.” regions or groups system, a view echoed by Anthony Oxitec’s Alphey is hopeful that his of countries using James, who is working on popula- non-propagating, non-biting (because GM technology tion replacement at the University of they are males) GM mosquitoes will be California: “If any one of these GM given the “thumbs-up”, but he is well integrated with techniques works, we don’t expect it aware of the importance of winning other tools. will provide the solution alone,” he over the sceptics if GM-based steriliza- Luke Alphey says. “We are going to have to develop tion is to become a significant public a very strong integration of the com- health tool. “We have to provide the ponents of [mosquito-borne disease] necessary information to allow the In recognition of WHO’s role eradication: vector control, vaccines scientists and technical advisers to gov- in providing guidance, a technical and drugs,” he says. ernments in affected countries to decide consultation will be held in May in And as Eggleston points out: “The whether this is right for their country Geneva to assess the current status problem isn’t going to go away. Global and circumstances,” he says. and discuss future plans for develop- warming is having a real impact, with Those local scientists should also ing GM mosquitoes as a control tool. the encroachment of mosquito-borne be involved in the development of Co-organized with the Foundation for diseases on new territory, including the technology so that they can help the National Institutes of Health, the southern Europe.” ■ 168 Bull World Health Organ 2009;87:167–168 | doi:10.2471/BLT.09.020309.