Transgenic mosquitoes.. good or bad

What is dengue?

Dengue fever is an illness caused by an RNA flavivirus spread by the bites of mosquitoes. The symptoms include fever, headache, rash, severe pains in the muscles and joints, and pain behind the eyes. Dengue fever is rarely fatal, while the related dengue haemorrhagic fever is a severe disease that leads to death in approximately 5 percent of cases. Dengue hemorrhagic fever is seen most often in children younger than 15 years old. It is also seen most often in individuals who were previously infected with simple dengue fever.

The dengue flavivirus occurs in four different serotypes, DEN-1, DEN-2, DEN-3, and DEN-4. Contracting one form of dengue fever provides lifelong immunity from that serotype, but not from the other serotypes. Cases of dengue fever occur primarily in urban areas in the tropics. Humans contract dengue fever from bites of infected female mosquitoes of the genus Aedes . Aedes aegypti is the primary vector in most regions. When a female Aedes mosquito bites a person infected with dengue, the virus incubates in the insect body for 8-11 days, after which the mosquito can spread the disease to other humans for the remainder of its life span (15-65 days). Once the virus enters a human, it circulates in the bloodstream for two to seven days, during which time the virus can spread. Aedes albopictusis was originally the primary vector of dengue fever, and remains a major vector in Asia. The species has recently spread to Central America and the US, where it is a secondary vector of the disease . Aedes aegypti is primarily urban, and Aedes albopictusis rural, thereby increasing the ecological range of habitats in which people can become infected. Humans are the primary reservoir for the virus.

In recent years, dengue has spread extensively in North and South America. In Mexico the number of dengue cases increased 600 percent between 2001 and 2007. In 2007 alone, there was a 40 percent increase in dengue cases. The disease has also spread to Hawaii and along the border in Texas. Even though the impact of climate change on the increased incidence and spread of dengue is less obvious than is the increase of malaria, it is reasonable to assume that global warming will greatly extend the range of the virus disease, though this assumption has been contested.

The blueprint for exterminating mosquitoes

Exterminating the mosquito vector is the preferred approach to controlling dengue according to those promoting genetic modification of mosquitoes. The Stanford Business School proposed that releasing genetically modified (transgenic) male mosquitoes could eliminate dengue fever and other mosquito-borne diseases within a year in communities of up to a million people. Stanford Business School is promoting the work of researchers at Stanford's Institute for Computational and Mathematical Engineering, and Oxford University and London School of Hygiene and Tropical Medicine in the UK. The technique employed is called “Released Insects with a Dominant Lethal” (RIDL), a variant of SIT. The dominant lethal male mosquitoes developed for RIDL are more sexually attractive to female mosquitoes than the dominant lethal males produced by X-irradiation , and they cause death of the progeny during the late larval stages, thereby allowing the transgenic larvae to compete with the normal insect larvae for food. The mathematical model analysing the control of mosquito-borne diseases by a RIDL predicts eradication of dengue disease in one year.

The mathematical model cannot be trusted to make reliable predictions, however, simply because the genetics and even more so, the ecology and host-parasite relationship of dengue disease are complex and poorly understood; in particular, there are silent as well as overt infections. More seriously, the optimistic mathematical model says nothing about the genetic modification involved in RIDL, and there lies the devil in the detail.

Millions of transgenic mosquitoes are to be released into the fishing village of Pulau Ketam off Selangor, Malaysia, as part of an international series of field trials to fight dengue fever. The Malaysian field trials will be undertaken by the Health Ministry's Institute of Medical Research (IMR) in collaboration with Oxitec Ltd., a spin-off biotech company from the University of Oxford in the UK. This follows the reported success of confined laboratory trials conducted under the supervision of the IMR over the past year.

The technique, which has won Oxitec the Technology Pioneers 2008 award at the World Economic Forum, involves releasing transgenic male Aedes mosquitoes carrying a ‘killer' gene to mate with wild female mosquitoes, which causes (nearly) all their progeny to die. This is a variant of the Sterile Insect Technique (SIT) that has been successfully used in wiping out other insect vectors in the past, though the sterile males were created by X-irradiation, and not by transgenesis.

The release of sterile males is considered “environmentally benign”, as only female mosquitoes bite and suck blood and transmit the disease-causing virus; not the male mosquitoes.

If the Pulau Ketam trials are successful, the transgenic killer mosquitoes will be released in bigger towns which have a high incidence of dengue. Dengue is reported to be the fastest growing vector-borne disease in the world, affecting 55 percent of the global population with an estimated 100 million cases in over 100 countries. Chikungunya, a disease similar to dengue fever and also spread by the Aedes mosquito, has become a major problem, at least in India, where there were 140 000 cases in 2007.

Oxitec has received regulatory and import permits for confined evaluation in the US, France and Malaysia, while still holding discussions with regulators of other endemic countries such as India.

Environmental groups fear that releasing the transgenic mosquitoes may affect the ecosystem and cause further damage. But there has been remarkably little informed reporting on the nature of the potential hazards involved.
Part two tomorrow