'Grounded' mozzies may halt dengue

BBC News reports that “scientists are breeding a genetically altered strain of mosquito in an effort to curb the spread of dengue fever”. The dengue virus is carried by Aedes aegypti mosquitoes in tropical and sub-tropical regions, and spread by the female mosquitoes when they bite. Dengue affects up to 100 million people a year and there is no vaccine or treatment for the infection.

The researchers in this study carried out genetic modifications on Aedes aegypti mosquitoes that resulted in preventing the wing muscles in the females from developing. The affected females cannot fly, making them susceptible to predators and unable to find a mate or feed.

The researchers’ aim is to reduce wild mosquito populations by releasing genetically modified male mosquitoes back into the wild, whose female offspring will be affected, thereby in time reducing the populations that carry dengue.

This research shows promise as a method of controlling Aedes aegypti populations, but further studies will be needed to determine how well the genetically engineered male mosquitoes compete with normal male mosquitoes in the wild for mates, and how well they suppress wild mosquito populations.

Where did the story come from?

The research was carried out by Dr Guoliang Fu and colleagues from Oxitec Limited, and the Universities of Oxford and California. The study was funded by the Foundation for the National Institutes of Health. The paper was published in the peer-reviewed scientific journal: Proceedings of the National Academy of Sciences of the USA .

BBC News gives accurate and balanced coverage of this study.

What kind of research was this?

This was laboratory research in mosquitoes, looking at whether researchers could develop a way to control the Aedes aegypti mosquito population. This mosquito lives in tropical and subtropical areas, and is the main carrier of the dengue virus. Dengue infection causes a severe flu-like illness, and can develop into potentially fatal dengue haemorrhagic fever.

There are currently no vaccines or specific drugs for treating dengue, so controlling the mosquito population is the main way of preventing the disease. The life cycle of the mosquitoes begins in water where the adults lay their eggs. These eggs hatch into larvae, then develop into pupae, from which the adults emerge. Most existing prevention strategies aim to remove containers where water can collect and the mosquitoes can breed, and use of insecticides.

Another strategy trialled in the 1970s was the release of sterile mosquitoes into the population. However, this technique has not become widespread due to practical problems, such as the need for irradiation facilities to sterilise the mosquitoes, difficulties in transporting adult mosquitoes, and problems in isolating only male mosquitoes for release (as males do not bite).

The researchers in this study wanted to see if they could genetically alter the mosquitoes in a way that would not affect male mosquitoes and selectively kill adult female mosquitoes. This would make it possible for mosquitoes carrying the genetic alteration to be transported at egg stage rather than as adults, and would allow the altered eggs and larvae to “compete” with normal larvae, but the adult females would die and therefore not be able to spread disease. This type of study is an important step towards developing ways to control the spread of dengue.  It may also lead to ideas for controlling other mosquito-borne diseases, such as malaria.

What did the research involve?

The researchers targeted a gene called Actin-4 that is involved in the development of muscles used in flying, and is active in female Aedes aegypti mosquitoes, but less active in males. It was predicted that the loss of these muscles would impair the adult female mosquitoes’ ability to fly. This would make it difficult to escape the water once they emerged from the pupa, making them more susceptible to predators, and unable to locate a mate or to feed.

In the laboratory, the researchers isolated the piece of DNA that controls the activity of the Actin-4 gene (called a promoter). This DNA contains instructions that allows the gene to be switched on in developing flight muscles in females, but not in other cells or in males.

The researchers then genetically engineered mosquitoes to carry this promoter attached to a particular gene. When this gene was switched on in the developing flight muscles of female mosquitoes, it would cause the muscle cells to die, making the female mosquitoes unable to fly.

Various experiments were carried out to test whether this gene was expressed only in the flight muscles, and in females, and what effect it had on flight in adult females. Further modifications were made to reduce any chance of this mechanism being expressed in male mosquitoes. The adult mosquitoes’ ability to fly was tested by hatching the pupae in individual water-filled containers, and then gently shaking the containers to see if the adults could take off from the water.

What were the basic results?

The researchers succeeded in switching on the lethal genes in the flight muscles of female and not male mosquitoes. Almost all (99–100%) of the adult female genetically engineered mosquitoes could not fly. Most of the genetically engineered male mosquitoes (about 97–98%) could fly.

How did the researchers interpret the results?

The researchers concluded that they had developed a method of producing genetically engineered flightless female Aedes aegypti mosquitoes. This genetically engineered strain of mosquitoes could be distributed as eggs rather than as adult mosquitoes, which should make distribution easier and cheaper, and allow community involvement. They say that “these strains are expected to facilitate area-wide control or elimination of dengue if adopted as part of an integrated pest management strategy”.

Conclusion

This research has shown that it is possible to genetically engineer the Aedes aegypti mosquito to produce females that cannot fly, and therefore cannot feed or mate, but leave males unaffected. The logic is that if these male genetically engineered mosquitoes are introduced into the wild and breed with normal females, the female offspring will not be able to reproduce, and this should reduce the wild mosquito population.

The researchers acknowledge that further tests will be needed to determine how well the genetically engineered male mosquitoes compete with normal male mosquitoes in mating, and how well they suppress wild mosquito populations. In addition, further studies are needed to look at whether these techniques could be applied to other mosquito species. The fact that malaria is spread by more than one type of mosquito means that it may be harder than dengue to tackle using this approach.