TWN briefing on GM mosquitoes

Dengue is a very serious problem, not only in Malaysia, but also in many other countries. In a bid to address this issue, genetic engineering has been carried out on the mosquitoes that carry this disease.

 

The National Biosafety Board (NBB) has recently granted approval to the Institute of Medical Research (IMR) to release genetically engineered (GE) male Aedes aegypti mosquitoes (OX513A) in Malaysia for the purpose of a field experiment. The field experiment aims to compare and evaluate the longevity and dispersal distance of the GE male mosquitoes in comparison to the wild type (non-GE) mosquitoes.

 

If the experiment is successful, the GE mosquitoes may later be used as part of a programme to curb dengue in Malaysia. The GE mosquitoes have been genetically engineered to include two new traits, fluorescence and conditional lethality. The fluorescence trait acts as a marker for the GE mosquitoes. When the GE male mosquitoes mate with females in the wild, the conditional lethality trait will be passed on to the offspring and the resulting mosquito larvae will die, although this will only happen in the absence of the antibiotic tetracycline.

 

The release sites identified are Bentong district in Pahang, and Alor Gajah district in Melaka. There are two release phases planned for each location – the first phase at an uninhabited site (0.5-1 km from the nearest human population) and the second phase at an inhabited site.

 

The release at both uninhabited and inhabited sites would involve either approximately 2,000-3,000 GE mosquitoes a day for two consecutive days, or a single release of approximately 4,000-6,000 GE mosquitoes. The experiments may be repeated.

 

Assuming that 4,000-6,000 GE mosquitoes are released at each phase of the experiment (uninhabited, inhabited and at each release area), this means that a total of 16,000-24,000 GE mosquitoes could be released into the environment of Malaysia (more, if the experiments are repeated). These experiments could be taking place as early as December 2010.

 

 

 

Although the experiment aims to release only male GE mosquitoes, there is a possibility that the sorting process to select the males may not be fully accurate or effective, especially with the large numbers involved. The available information provided by the government does not indicate whether the reliability and efficiency of the sorting process can be guaranteed.

 

In addition, an unspecified number of non-GE mosquitoes will be released in the experiment, but no information is provided to the public as to whether this will also be males-only.

 

Accidental release of female mosquitoes would raise additional concerns as they could transmit dengue. Only female mosquitoes bite and take blood meals, whereas male mosquitoes do not.

 

 

The mosquito larvae that are produced after the GE males mate with females will only die if they do not encounter tetracycline in the environment. Tetracycline is a fairly common antibiotic used in animal husbandry and for medical and veterinary purposes.If tetracycline is present in the environment, there will be a reduction in the effectiveness of the conditional lethality trait, resulting in an increase in survival of the GE larvae.

 

The use, presence and persistence of tetracycline in the environment at the proposed release sites needs to be assessed, and the terms and conditions attached to the approval given to IMR stipulate that this must be done before any release occurs.

 

Reassurances have been given that when the GE male mosquitoes mate with wild females, the resulting offspring will die, as that is the whole point of the GE mosquitoes. However, a small percentage of the larvae will survive. According to the published literature, even under controlled laboratory conditions, 3-4 percent of the larvae survive to adulthood. As genetic expression is known to vary greatly in response to environmental conditions, the percentage of larvae surviving in the field may be greater.

 

There could therefore be persistence of the GE mosquitoes in the environment, a proportion of which would be females and capable of transmitting disease. While the levels may be low, and there may or may not be epidemiological significance to the communities exposed in the inhabited field release sites, a quantitative estimation of the risk of additional disease burden must be made.

 

 

Aedes aegypti is not native to Malaysia, but is an introduced, invasive species. Nonetheless, it has become part of Malaysia’s complex ecological ecosystem. It would be important to consider the implications on other species that interact with Aedes aegypti in the receiving environment.

 

This could include effects on food webs and ecological functioning or impacts on the abundance of other species that feed on mosquitoes. Additionally, if there is horizontal gene flow to non-target species, the genetic elements that induce sterility could increase ecological harm.

 

The available information provided does not indicate whether there are baseline ecological data on mosquito and other ecology in the proposed release sites. This information is necessary in order to make informed decisions.

 

 

IMR has proposed control measures to prevent the GE mosquitoes from persisting in the environment, and the terms and conditions attached to the approval have extended both the scope and time period for the control measures. However, the monitoring of these mosquitoes is dependent on the adequate functioning of the fluorescence marker gene. Because genetic expression can vary, the production of the fluorescent marker may be diminished and some GE mosquitoes may not be identifiable by fluorescence. If this happens, the GE mosquitoes may persist in the environment without our knowledge.

 

Therefore, an assessment must also be made as to whether the monitoring plan is adequate and whether complete removal of GE mosquitoes and larvae from the field release sites is possible.

 

 

As the experiments are also proposed for inhabited sites, local communities living in these areas have the right to be specifically informed, consulted and their consent obtained before any field release occurs. The terms and conditions attached to the approval stipulate the mandatory obligation to obtain the prior consensus and approval from the inhabitants in the release sites.

 

However, it must be ensured that this process is carried out in a fully transparent and balanced manner. Will IMR be conducting the public forum for this purpose? If this is the case, there will be a clear conflict of interest.

 

 

The risk assessment and regulatory experience for GE mosquitoes worldwide is not very mature yet and international organizations such as the World Health Organization and the Cartagena Protocol on Biosafety are only now developing guidance or have only recently completed guidance on these issues.

 

While there have been field trials carried out in the Cayman Islands in 2009 and 2010 of this same GE mosquito, the receiving environment (both ecological and human) there is completely different from Malaysia’s and we cannot extrapolate from those releases to the Malaysian situation. A full evaluation of the risk assessment and monitoring reports from the Cayman Islands’ experiments should be made first by the international scientific community, especially to identify any unintended effects, before consideration of release anywhere else in the world.

 

In addition, while there has been longer experience with the environmental release of GE pink bollworm in the United States, this is an agricultural pest that is not involved in intimate contact with humans or disease transmission as Aedes aegypti is, and caution should be made in making a judgement on the safety of the release of the GE mosquitoes in Malaysia based on this.

 

 

This field release experiment is one of the first such environmental releases of these GE mosquitoes in the world. A much more precautionary approach is warranted for such a novel application. The authorities should reconsider the approval, in the light of the public health and environmental concerns raised. Alternative options could be explored, for example, conducting the experiments in netted areas that prevent the escape of the GE mosquitoes to the environment. All safety questions should be addressed first prior to any further experiments.

 

There also needs to be a much wider public debate on the issue than there has been to date, with further means of ensuring meaningful and effective public participation. The public consultation process initiated by the Ministry of Natural Resources and Environment via submission of views was an important first step, and it must be shown how the government has taken into account the comments of the public in its decision-making.

 

Additionally, there should be more emphasis on other effective, safe and affordable alternatives to dengue control. For example, research by the Forest Research Institute of Malaysia found that a number of essential oils such as Cymbopogon nardus (citronella grass), Litsea eliptica, Melaleuca cajuputi (gelam) and Cinnamomum spp. (cinnamon) demonstrate repellent properties against the Aedes aegypti mosquito. Euphoriaceae extracts, particularly Euphorbia tirucalli (firestick plant) has also been found to be an ideal larvicide against Aedes aegypti.

 

Efforts should also be stepped up on preventative practices, such as the elimination of Aedes aegypti breeding grounds, to tackle the dengue scourge in Malaysia.