Defeating dengue with GM mosquitoes

Dengue fever, which causes excruciating pain and death, is spread by the Aedes aegypti mosquito, which also carries yellow fever. Originally native to Africa, the insect spread throughout the world following the second world war, and is now found in over 110 countries. As a result, incidence of dengue fever has risen 30-fold in the last 50 years, and now costs the world an estimated £3.5 billion annually.

Because no vaccine or specific drug yet exists, attempts to halt the disease’s spread have relied - with little success - on control of the Aedes aegypti mosquito through pesticides and education. Decades ago, US scientists began to produce sterilised male insects in the hope that their introduction to the wild would reduce the number of offspring and decrease incidence of dengue. The theory was revolutionary, proving successful against some agricultural pest insects, but the radiation used to achieve sterility had adverse effects on mosquitoes.

Inspired by the concept, Professor Luke Alphey at the Department of Zoology developed a genetic modification technique which stymies the reproduction of the mosquitoes. In order to develop beyond larval stage, the offspring of Alphey’s modified male mosquitoes require an antibiotic called tetracycline, which is impossible to obtain from natural sources in their habitat.

When released into the wild, these males mate with females and their offspring never develop into adults. The result is a targeted and gradual decline in the population of the Aedes aegypti species wherever it is introduced. The concept was patented in 1999, and then developed into a commercial spin out called Oxitec Ltd in 2002.

As with any GM technology, Oxitec has received criticism. But, unlike other GM products, these mosquitoes don’t spread their genes down the family line or to other species. What’s more, Oxitec is confident that, as an alien, invasive species in most dengue-endemic countries, their eradication does no harm to the ecosystem.

It’s not just speculation, either. Oxitec has already conducted field trials in in Brazil, Malaysia and the Cayman Islands with great success, and long-term trials are now taking place in Brazil in collaboration with Moscamed, an organisation founded to develop sterile insect control in Brazil. Since June 2013 a project has been underway in a town of 50,000 people, demonstrating the confidence that the Brazilian authorities have that GM mosquitoes represent their best chance of bringing dengue under control. Panama has begun an evaluation of Oxitec’s mosquitoes to see if the approach will prove equally effective there. In addition, Alphey’s research has had a major impact on the development of regulatory frameworks around the release of GM insects, prompting a thorough consideration of issues such as quality control and proper risk assessment.

The work won Oxitec the Wellcome Trust Translational Award in 2011, and in March 2014 Luke Alphey won both the social innovator category and ‘Innovator of the Year’ at the BBSRC’s Fostering Innovation awards. Oxitec was acquired by Intrexon in 2015 for $160 million

The long-term goal the company has set for itself is to reduce populations of disease-carrying mosquitoes by over 80% for as little as £3 per person per year in the areas in which the technique is used. If it can achieve that, dengue fever may well become a disease of the past.

Research funded by BBSRC and the Wellcome Trust. This case study if part of the Oxford Impacts series.