Genetically engineered Aedes aegypti mosquitoes: Are there risks? By Third World Network

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.

What are some of the concerns?

1) Could female mosquitoes be accidentally released?

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.

2) Could GE larvae and mosquitoes survive and persist in the environment?

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.

3) Could there be adverse effects on other species in the ecosystem?

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.

4) Are the monitoring and control measures proposed adequate?

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.

5) How will the prior informed consent of local communities at the release sites be obtained?

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.

6) Is there sufficient risk assessment and regulatory experience?

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.

 

Some concluding thoughts

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.

This briefing paper (22 November 2010) was prepared by Third World Network. For further information, please contact twnkl@twnetwork.org

 

GM mosquitoes will fail, and incur heavy costs

Nov 19, 10

Dr Lim Thuang Seng, an immunologist appeals to the government to seriously reconsider their intention to release genetically modified mosquitoes in Pahang and Malacca. Dr Lim said this experiment will not lead to any solution in eliminating the aedes aegypti mosquitoes in Malaysia, but to put Malaysian in unnecessary potential health risks.

Dr Lim said although there was unofficial claim that experimental study on GM mosquitoes releases in Cayman island to eliminate aedes aegypti was a success, Dr Lim however, doubted how long the island will remain aedes aegypti free without continuous release of these male GM mosquitoes since the company that developed this GM mosquito claimed the male GM mosquitoes will die within a few days.

Dr Lim also described the experiences of Cayman Islands in combatting the dengue transmitting aedes aegypti mosquito. Cayman Islands, a British Overseas Territory in the Caribbean, started its mosquitoes elimination efforts way back in early 1950's using the then still approved method of 5 percent DDT. Success was achieved and subsequence surveys confirmed the Grand Cayman Islands was free of aedes aegypti.

In 1965 with the objective of promoting tourism, Cayman undertook another campaign to control the Grand Cayman Islands' nuisance mosquitoes including the dengue transmitting aedes aegypti mosquitoes.

In 1966, the Mosquito Research and Control Unit (MRCU) established a network of ovipots and CO2 baited traps on the Grand Cayman Islands to detect and monitor the presence of aedes aegypti. No aedes aegypti were detected but subsequence surveys found presence of the mosquitoes in two other sister islands.

After the ban on the use of DDT, the Cayman Islands government used a 3-pronged strategy in controlling the mosquitoes population in the island that included:

a) Prevention of entry through disinsection of ships and planes entering the island,

c) chemical control.

Successes were achieved despite reintroduction of the mosquitoes in 1973, 1980 and early 1990's.

However, these re-emerged mosquitoes were subsequently eliminated. Today, Cayman Islands continues to face the threat of dengue transmitting aedes aegypti mosquitoes with evidence of aedes albopictus becoming established in some cities where aedes aegypti was eliminated.

Dr Lim said, from the Cayman Islands experiences in combatting aedes mosquitoes, he believed the traditional methods of controlling mosquitoes used presently by the Health Ministry are effective enough if practised in combination and implemented persistently.

Dr Lim explained that the Grand Cayman Islands with a land area of 200 sq km and surrounded by sea though effective in eliminating aedes aegypti, failed to prevent reintroduction of the mosquito from external sources.

How can peninsula Malaysia with a much bigger land area and border with tropical Thailand in the north and Singapore in the south with close proximity Indonesia in the west, prevent the reintroduction of the mosquitoes?

Dr Lim further explained dengue fever is transmitted by aedes aegypti and aedes albopictus and the Cayman Islands' experiences indicated when aedes aegypti is eliminated in one area, the possibility of the area being taken over by aedes albopictus cannot be ruled out even though albopictus is predominantly found in forest areas.

Dr Lim said genetic modification of mosquito genome has been going on for more than a decade, and it had raised concern from the scientific community as well as the public.

The issue we Malaysians face today is not about whether the male GM aegypti will mate in the wild and produces non-viable progeny, it is also not about how long the GM mosquitoes will survive in natural environment, but more about the existing unpredictable consequences of mutation of these GM mosquitoes which according to the company that developed it, suggested it requires the continuous release in enormously large number of these GM mosquitoes into our environment in order to be effective in eliminating the aegypti mosquitoes in Malaysia.

Given our geographical and environmental setting as a tropical country with half a year of heavy rain fall, the GM mosquitoes' mission is destined to fail.

Recent reports on the emergence of two new malaria-transmitting mosquitoes with similar physical but different genetically from the normal African anopheles gambiae also suggested the GM aedes aegypti may require genetic adjustment should similar mutation occur in aedes mosquitoes and that the abundant usage of tetracycline especially in animal farming industry may render the lethal tetracycline gene in GM mosquitoes ineffective faster than we thought.

It is not known what would happen when we release a large number of GM mosquitoes into the environment, whether all the GM mosquitoes will die as planned, or will a few manage to survive and multiply.

Are we absolutely certain that all larva or pupa will not develop into adult mosquitoes and will the GM mosquitoes or their lava or pupa not mutate? With all these uncertainties, can we trust the company that they can recapture all the GM mosquitoes that were released into the wilderness?

Dr Lim believes the potential danger to Malaysian of a natural aedes mosquito mutating to overcome a new insecticide is far less than the potential danger of a GM mosquito that has received additional DNA and mutated.

Finally Dr Lim hypothetically pointed out that assuming the GM mosquito is effective in eliminating all aegypti mosquitoes, dengue will continue to be transmitted but by aedes albopictus and in order to maintain the country aegypti free, continued release of GM mosquitoes is needed. In other word, the government will need to continue to spend a lot of money to keep the country free of aedes aegypti while cases of dengue continues to threaten the health of Malaysians

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Genetically modified mosquitos: Boon or bane?

COMMENT PETALING JAYA: Mosquitos, tiny in size and deadly in their bites, have been around for millions of years. And they continue to be a scourge in modern times.

But now there is hope that the Aedes threat can be tackled through the aid of genetic science. Next month, about 4,000 to 6,000 genetically modified (GM) mosquitos will be released in Bentong, Pahang and Alor Gajah, Malacca, in a bid to reduce the Aedes population in those areas.

These male mosquitos are of the Aedes Aegypti strain.

The project is undertaken by the National Biosafety Board, which had initially planned to release the GM mosquitos in October but was postponed.

If everything worked out as planned, the GM male mosquitos will mate with the female strain, and the progeny will die before they can bite and transmit disease. This way, the Aedes population can be reduced, lessening the threat of a dengue outbreak.

The idea itself sounds admirable and noble in nature. Dengue fever kills millions of people across the globe every year and any effort to curb its spread should be supported by the public. However, before we launch a full-scale war on the mosquitos, we must ask this vital question: How much do we know of mosquitos?

For a start, mosquitos had been around for about 60 million years. The tiny insect, the size of a grape seed, had survived the Dinosaur Age, Ice Age, Stone Age, Industrial Age and is now thriving in the Information Age. It had lived through the destructive forces of nature and adapted itself effectively through all the climatic changes as well.

 

Distinct features

Mosquitos had wiped out legions of army before and killed great leaders of the past. Even Alexander the Great was suspected to have succumbed to malaria, a disease carried by the Anopheles mosquito.

Currently, there are more than 3,000 types of mosquitos living across the globe. Each type has its distinct features. Coming back to the Aedes, the female mosquito can lay about 100 eggs at one time. Once the eggs are hatched and the offspring turns into adult, the young male will be able to identify its mate within a distance of about one inch, based on the different style of wing beats both genders possess.

Once they have identified one another, both mosquitos will energise themselves by consuming nectar from the flower plants before mating. The female will then seek its first blood meal (human blood) in order to provide enough nutrients for its eggs. Later, it will lay its eggs and that is how a life cycle of an Aedes works.

Normally, a male Aedes lives for three days and the female for about a month. The latter can consume between three and six blood meals and lay eggs to about three times its lifespan.

Knowing that, let us pose a few questions on how effective the GM mosquitos are in reducing or wiping out the Aedes' progeny.

How do we actually get the GM male to mate with the female? We know that both male and female recognise one another by the unique wing beats that only they possess. So if the GM mosquitos' wing beats do not match with the Aedes' natural "rhythm", would the female mosquitos be "interested" to mate with the GM mosquitos?

Then there is the question of distance. As they only mate when they are about one inch apart, the entire project would fail if the GM mosquitos are released even one metre away from the females.

Assuming the GM strain and the female were successful in mating, Third World Network's (TWN) senior researcher Lim Li Ching in August raised concerns that its progeny will only die in the absence of an antibiotic called tetracyline.

However, tetracyline is prevalent in Malaysia as it is used for medical, agricultural, veterinary and livestock purposes. Therefore, if the eggs are laid in an area exposed to this antibiotic, its progeny may live and we may end up having progeny of GM mosquitos running loose in the environment.

As it is, mosquitos are very skilful in adapting themselves. Hence, a GM mosquito's progeny may have increased survival skills. In addition, mosquitos are known to be the link between several diseases (pathogen) and the human race.

With GM mosquitos running loose, it may bring another unknown disease to the human race due its newly acquired trait. It is not something new as the Japanese Encephlitis (JE), spread by mosquitos, was a relatively new disease in the medical world.

One expert claiming anonymity, asked: "Why are mosquitos not able to transmit the HIV virus despite the fact it can be be passed on by exchange of bodily fluid?"

But a scary possibility exists: mosquitos, being highly adaptable, may mutate into a new strain complete with the missing enzyme which can make it an HIV carrier.

"When that happens, all hell will break loose,"said the expert. He fears that even if the government succeeded in wiping out Aedes, another strain will take its place and create a new health hazard.

Assuming the project does take place and the government decided to go nationwide with it, a lot of problems in terms of logistics and contigency plan needed to be settled.

For example, the male mosquito can only live for three days, making it "highly perishable goods".

 

Who will monitor?

Oxitec, a biotech company based in Oxford, England, which is in charge of the Malaysian project, will need to produce billions or maybe trillions of these mosquitos for every district or even residential areas across the nation. Does it have the capacity to do so?

Oxitec needs to load and release the mosquitos within three days. Hence, a lot of work will have to be done: producing the mosquitos, packing them safely, and transporting and releasing them. And all these must be carried out according to strict healthcare guidelines. And somebody has to monitor it. Who is going to keep tabs?

Besides, if there are any flaws in the system or if something goes tragically wrong, who will be responsible? And what are the government's contigency plans to handle any shortcomings or worse still, the real possibility of an outbreak of a new type of vector-borne disease? All these questions have yet to be answered.

Mosquitos are dangerous, bloodthirsty pests and we know very little about them. For instance, do we know where mosquitos hide during the day?

"The answer is, nobody knows. That is how much we know about mosquitos," the expert said.

On the commercial side, it was made known that the project was mooted by Oxitec. But there is not much information on its Malaysian operations.

Who are its Malaysian partners? How much funding it is bringing in? Has it obtained approval of the Malaysian Pesticide Board? Has it obtained a patent for GM technology?

According to information on the website, Oxitec was established in 2002 and it applies technology developed at Oxford University. Its speciality is conducting research on controlling vector-borne diseases. The British company claimed that its GM mosquitos, which are programmed for early death, can control the spread of dengue fever.

But for now, "Project GM" is the baby of the National Biosafety Board. Oxitech is kept away from the prying eyes of the public.

Ex-vector control staff, Malaysiakini.com

http://www.malaysiakini.com/letters/148492

In the letter "GM Mosquito: Stringent protocols in Place" of Nov 9, 2010, Madam Yamuna Perimalu, writing on behalf of the corporate communications unit of the Ministry of Natural Resources and Environment, describes the lengthy (5-year) process that has occurred to develop the present proposal to release Living Genetically Modified (GM) aedes aegypti mosquitoes in Pahang (Bentong district) and Malacca (Alor Gajah and Malacca districts) and attempts to assure us that all issues raised have been thoroughly addressed.

It should be pointed out that the Malaysia Biosafety Act was only approved in 2007 and only came into force in 2009. What safeguards were in place during the unregulated years?

The development of a GM mosquito is certainly a scientific and technological tour-de-force and the accomplishment needs to be appropriately recognised as such. However, what is most disturbing about the present planned release of GM aedes aegypti mosquitoes is the lack of information and further approvals associated with the proposed release as outlined below.

1. Why is the Ministry of Natural Resources and Environment spearheading this undertaking? Doesn't mosquito and mosquito vectored disease control fall under the purview of the Ministry of Health? Why is the Ministry of Health silent in this entire matter?

2. What commercial entity is undertaking this endeavour and who are the individuals involved? There has been no disclosure of what and who is supporting the GM mosquito and its release (other than the Institute for Medical Research, IMR).

Who is going to produce the GM mosquitoes, who will release them, who will account for them and who will assume responsibility for any untoward events that occur? When it comes to larger scale release, billions of male mosquitoes will be required to be released - who will produce them and be accountable?

3. In the United States, any release of a genetically modified organism that involves humans requires an Institutional Review Board review of the proposed release and signed informed consent of all individuals exposed to the genetically modified organism.

How will informed consent be obtained from all individuals potentially exposed - not just from a few isolated individuals - or are Malaysian lives not nearly so dear to our government? And shouldn't the review committee include Institute of Medical Research and the University that has an entomology department such as Universiti Putra Malaysia and the vector division, Ministry of Health to offer the opinions and advice?

4. The GM mosquito is designed to control wild mosquitoes that are classified as a "pest". All materials engaged for the control of mosquitoes are consequently classified as "pesticides" and require registration and approval from the Malaysia Pesticide Board. There is no mention that such registration and approval has been requested or obtained.

5. Mdm Yamuna states that the USDA has approved the release of the GM pink bollworm and the GM fruit fly. This is true. However, these are agricultural pests and are not a threat to human health. To imply that the same level of criteria should be applied to GM mosquitoes, a known human blood feeder and human disease vector vastly oversimplifies the safeguards that need to be considered.

6. Mdm Yamuna further cites other countries, including India, as evaluating the GM mosquito. India has recently rejected the Genetically Modified eggplant - does the Ministry of Natural Resources and Environment really believe that India will then accept the GM mosquito?

7. It is stated that this is only the first step in a multi-step process of approval and is for only the proposed "limited" field trial. How long will the overall process require and how will dengue be controlled in the interim - how many Malaysians will become sick and how many deaths will occur?

8. Under Malaysian law, it is illegal to harbour, rear or propagate mosquitoes. With the GM mosquito, these activities are clearly occurring. Has the concerned business and people obtained an exemption from this law?

9. Are there other competing technologies that can also be considered, that are effective at controlling dengue-carrying mosquitoes?

The above are only specific questions regarding the release of GM aedes aegypti mosquitoes.

There are further more general questions (as described in the UNDP/World Bank/WHO Special Program for Research and Training in Tropical Diseases (TDR) publication 'Ethical, Legal and Social Issues of Genetically Modified Disease Vectors in Public Health' by Darrel Marcer).

1. Before field release of transgenic organisms, researchers must assess all the scientific and social issues associated with GM vectors and develop safety precautions to address potential risks.

2. The scientific and social risks should be minimised through careful design of the vector system, relevant laboratory experience, and careful choice of site including consideration of appropriate social and cultural factors.

3. Even if there are no perceived realistic risks, a procedure for their evaluation should be set up so that new information can be gathered and interpreted. This procedure may involve establishing a specialised ethical review committee to offer advice to researchers seeking guidance on the ethics of projects.

4. There should be prior environmental, medical and social studies for site selection, and the most appropriate site should be chosen based on the data obtained.

5. Information should be openly exchanged as broadly as possible to relevant community leaders, members of the community, and mass media. This needs to be done with international collaboration.

6. Consent should be obtained from the communities involved. Specific mechanisms for this need to be developed and will be useful for other areas of public health interventions.

7. A contingency plan for aborting field trials needs to be developed. One approach is to engineer a lethal gene for the vectors that can be induced by a non-toxic chemical to ensure total elimination of those that have acquired the genetic construct.

8. Commitment to the local communities involved in field trials should be made that they will be the first beneficiaries of more permanent use of a GM vector should the results indicate that its use is appropriate.

9. Intellectual property concerns should not be barriers to implementation of public health measures using GM vectors or their symbionts and/or pathogens. Prior negotiation, including possible involvement to allow access to the latest technology, is preferable to confrontation.

10. To avoid any suspicion by the public that could result in their rejection of this approach, governments should not involve partners from military research establishments in the projects.

11. The data should be open to all in order to benefit from global expertise and develop international consensus.

12. Whatever guidelines are developed, they should be revised as experience with genetic engineering technology grows, as knowledge of ecology and communities grows, and with societal trends.

Dr Marcer further emphasises that an international approach is required since vectors do not honor national borders, nor is their behavior always predictable.

Has the Ministry of Natural Resources and Environment fully followed all of these suggested guidelines?

No consideration of mosquito mating behavior and dengue virus transmission is reported by Madam Yamuna or the Ministry of Natural Resources and Environment. Mosquitoes have a complex mating behaviour which requires the male and female mosquito to come within 1 inch (2.54 cm) of each other before their wing beats harmonise in their mating ritual.

How will the laboratory-reared GM mosquito find its wild female partner? In the wild, the adult male mosquito emerges before the female and remains nearby so that when the females emerge, they can go and obtain a sugar (nectar) meal before host-seeking and mating. The GM mosquito has no clue where the wild females are. How will they find them - by sheer chance?

Madam Yamuna reports that simulated, contained field trials have successfully been carried out. At best, this is an artificial situation that bears no relation to the real world. When mosquitoes are contained in a closed environment, they have no choice and will eventually find each other and produce the expected result. In the wild, there is no containment and the likelihood of the GM male mosquito finding a wild female partner is dramatically reduced.

The dengue virus not only infects the salivary glands of the adult female aedes aegypti mosquito, but also the ovaries and eggs. When the eggs are laid, they are infected with dengue, which persists through the larval and pupae stages. Consequently, when the adult females emerge, they are already dengue positive and transmit the virus on their first (human) bite.

Even if they mated with the GM male Aedes aegypti mosquito, the wild female mosquitoes will still be positive for dengue and transmit the disease throughout their adult life cycle. Further, the wild male mosquitoes from the dengue infected eggs will also transmit the virus to any uninfected wild female mosquito that they mate with, thereby propagating the dengue virus to subsequent generations.

The GM adult male mosquito will soon die - usually within 3 days. How many mosquitoes, at what frequency of release and for what period of time will be necessary to control dengue with the GM mosquito?

 

What if it transmits HIV?

There is a famous quotation from the late Professor Andrew Spielman then at the Harvard School of Public Health:

"No animal on Earth has touched so directly and profoundly the lives of so many human beings. For all of history, and all over the globe, she has been a nuisance, a pain, and an angel of death. The mosquito has killed great leaders, decimated armies, and decided the fate of nations. All this, and she is roughly the size and weight of a grape seed" - from the Preface to Mosquito by Andrew Spielman and Michael D'Antonio (Harvard).

Since the mosquitoes are genetically modified, there is a high probability of it causing a new borne disease in the future and it is advisable not to disturb the natural eco system. Malaysia had its first dengue outbreak in Jinjang, Kuala Lumpur in 1972. Before that, it was unheard of and basically, the aedes mosquito had developed the new strain of disease.

There are many unknowns and unanswered questions concerning the GM mosquito. Science is very good at obtaining answers to posed questions. How do we know that we are asking the correct questions? In science, it is the questions that are not recognised and unasked that lead to the greatest problems.

For thousands of years, mosquitoes have been very clever at devising ways to overcome whatever mankind has thrown at them. What assurance can be provided that that is not the case with the GM mosquito? What would happen, for example, if the GM mosquito were to acquire the ability to transmit the Human Immunodeficiency Virus (HIV/AIDS)?

What assurances can the unidentified business and people provide that this will not occur? What would happen to the Malaysia tourist industry if some unanticipated consequence resulted from release of the GM mosquito - would other countries ban travel to Malaysia - would Malaysian's be banned from traveling to other countries? What would the economic consequences be - both for tourism and industry if that scenario arose?

The mosquito is quite literally the Most Dangerous Animal on the Planet! What is being proposed is the release of mankind's most mortal enemy. Can Malaysia afford to take that risk?

 

National Biosafety Board Decision

NATIONAL BIOSAFETY BOARD DECISION

APPLICATION FOR APPROVAL FOR LIMITED MARK-RELEASE-RECAPTURE OF Aedes aegypti WILD TYPE AND Aedes aegyptiGENETICALLY MODIFIED MOSQUITOES OX513A(My1)

NBB REF NO: NRE(S)609-2/1/3

APPLICANT: INSTITUTE OF MEDICAL RESEARCH

DATE OF DECISION: 5 OCTOBER 2010

The National Biosafety Board (NBB) on the 5 October 2010 made a decision to grant an approval with terms and conditions to the application from the Institute of Medical Research (IMR) for a field trial to release genetically modified (GM) male mosquitoes.

This approval permits the release of male genetically modified (GM) Yellow Fever mosquitoes, Aedes aegypti OX513A(My1) strain and male non-GM Aedes aegypti mosquitoes (wild type) to conduct a field trial entitled "Limited Mark-Release-Recapture (MRR)(1) ofAedes aegypti wild type and OX513A(My1). The proposed release sites are in Bentong, Pahang and Alor Gajah, Melaka.

The recommendation of Genetic Modification Advisory Committee (GMAC) to the NBB was for an approval with terms and conditions. Proper risk management strategies are to be followed as stipulated through the terms and conditions imposed (Appendix 1). Additionallyclose monitoring will be done to ensure that the terms and conditions imposed are implemented on the ground.

Public consultation for this application was done in August 2010 for a period of 30 days. Concerns raised by the public were addressed and taken into consideration when making the decision.

The basis of NBB decision is as follows:

The proposed field experiment is only for a limited small scale release and does not endanger biological diversity or human, animal and plant health when proper risk management strategies are followed as stipulated through the terms and conditions imposed with the approval. In addition, for the purpose of the field trial studies, the released male mosquitoes will be recaptured using standard procedures practiced by Ministry of Health;

 Risks identified for this field experiment were quite low in the context of a Limited Mark-Release-Recapture field trial. However, for a larger scale release, these risks will be re-evaluated;

 IMR has been very actively involved in GM mosquito research since 2006. Previous studies have already been conducted as laboratory experiments (contained use) and semi-field trials(2). This field experiment is the next phase of this research and an important prerequisite for any subsequent full scale release for population suppression;

 Only a small number of mosquitoes will be released in comparison to the existing wild population based on previous baseline population surveys conducted by IMR. In addition, the released GM mosquitoes have no selective survival advantage and will diminish through the process of natural selection;

 The proposed release site will be free from any dengue outbreak for at least 3 months before the start of the field trial and this will be verified by the relevant health authorities;

 Only male mosquitoes are released and male mosquitoes do not bite or carry the dengue virus. The Standard Operating Procedures for sorting the male mosquitoes for the release has been assessed and approved by GMAC. Sorting will be done mechanically, followed by a serial manual re-check on all the sorted mosquitoe pupaes by three highly trained laboratory technicians of IMR;

 Upon completion of the field trial, responsible site management is imposed to ensure that the area is completely cleared of any released GM mosquitoes. i.e. the monitoring period is extended and also additional fogging will be done to ensure that there are no residue GM mosquitoes in the environment;

 NBB, through the Department of Biosafety, will closely monitor the implementation of the field trial to ensure compliance at every stage of the release;

 Science based issues/uncertainties highlighted by researchers well versed with the issue were taken seriously and included in the scientific assessment by GMAC;

 Residents from the field trial site will be engaged in Public awareness activities and information about the field trial will be made available;

 Socioeconomic consideration including the number of deaths and the cost of medication due to Dengue were included. New technologies should be explored to complement the integrated pest management programme (IPM). The suppression of Aedes aegyptipopulation by incorporating biotechnology in the IPM is promising; and

 Cayman Island has already done a field release of this GM mosquito and there were no issues caused by the release. Other countries such as United States of America (Colorado), Thailand, Brazil and India are involved at contained use experiments involving GM mosquitoes. Countries like Singapore and Vietnam are reviewing this technology involving GM mosquitoes.

Additional Information:

Issues to be addressed for future big scale releases:

o Release of transgenic mosquitoes may cause other pests to become more serious;

o Increase in the population of another mosquito species due to suppression of the target mosquito;

o Stability of the transgenes(3) in the field;

o Behaviour of GM mosquitoes in the field;

o Sorting error when handling large quantities of GM mosquitoes to be released; and

o Establishment of an effective IPM to incorporate the new GM technology.

(1)Note: Mark-release-recapture (MRR) is a technique whereby a number of organisms/animals are marked in a way that makes them easily recognized when they are encountered again within a habitat. It is assumed that the marked organisms/animals that are released will mix back into the rest of the local population.

(2)Note: Semi field trials - experiments conducted in a Temporary Contained Trial Facility at IMR - a fully contained structure, simulating the living space for a household of 2-4 people in Kuala Lumpur.

(3)Note: Refers to the new genes incorporated into the GM mosquitoes

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TERMS AND CONDITIONS FOR CERTIFICATE OF APPROVAL

Information and/or documentation that should be submitted to NBB at least two weeks prior to the start of field trials

a) Documentation from District Council/Majlis Daerah or relevant authorities on the presence or otherwise of aquaculture, poultry and pharmaceutical industries within a vicinity of 500 meters of the release sites, and information on whether any of these industries regularly use tetracycline in their operations is related to the concern that there may be residual tetracycline around the release sites.

b) Confirmation from the relevant health authorities that the sites selected has been free from any dengue outbreak for at least 3 months before the start of the field trial.

c) Detailed information on the positioning of the ovitraps and BG-Sentinel traps (documentation on setting-up of traps, including GPS information and photographs has been proposed by the applicant). Proper cautionary measures should be taken to ensure that that traps are positioned at suitable locations/heights for effective trappings.

d) A consent letter should be provided from the Local Council for the district/s where the release sites are located for the proposed MRR field trial.

e) Public Notification and Consensus - It is mandatory that the applicant through a public forum obtains prior consensus and approval from the inhabitants in the release sites regarding the proposed MRR field trial.

Part B

Actions to be taken and reported to NBB during /after the field trial

a) All proposed activities and methods submitted in the dossier and agreed upon through other means of communication with the applicant should be appropriately and responsibly adhered to.

b) Sex sorting must be carried out in compliance with the SOP submitted (SOP for Sex Sorting of Aedes aegypti Mosquitoes). Additionally, all OX513A(My1) mosquitoes for release must be checked and not merely a 'quality control sample'.

c) All extra insects/ recaptured insects are to be transported in shatter-proof double-covered cont for subsequent identification, analytical studies or appropriate disposal (according to SOP at IMR).

d) At the end of the field trial, fogging for a 400m radius is required according to the Ministry of Health's guidelines and a clean-up operations (gotong-royong) should be conducted to eradicate all breeding grounds. A second fogging should be conducted one week after the end-of-field-trial fogging.

e) At the end of the field trial (first fogging), applicant is required to continue monitoring for another month to ensure no residual OX513A(My1) strains are left behind. The traps should be checked on a daily basis. During this additional one month monitoring period, fogging should be done if any residual OX513A(My1) is detected.

f) Upon completion of the open field trial, a comprehensive report should be submitted to the National Biosafety Board within two months from the end of the trial.

Department of Biosafety, Malaysia