Attack is the best defence... against dengue, which affects 50 million worldwide yearly. The authorities believe the war can be won by attacking the carrier, the Aedes mosquito. The plan to unleash genetically modified
mosquitoes on Pulau Ketam, however, has raised fears of monster mosquitoes wreaking havoc worse than dengue. Experts explain the plan to JUNE RAMLI and ANNIE FREEDA CRUEZ

THE best way to prevent dengue is to prevent mosquito bites. And that means keeping the Aedes mosquito at bay.

"The use of insecticides and mosquito nets is not practical as the mosquitoes bite at dawn and early evening. Another way is to look for breeding sites and reduce the number of mosquitoes.

"That is the key for dengue control, but it is not cost effective and is very labour intensive," said Datuk Professor Dr C.P. Ramachandran, the chairman of the World Health Organisation's global programme for the elimination of lymphatic filariasis (commonly known as Elephantiasis) technical advisory group.

He said this was why a method using biotechnology was sought, even as the pharmaceutical industry tried to develop an anti-viral drug for the disease, which kills about 100 annually in Malaysia.
Under the biotechnology induced plan, transgenic male Aedes mosquitoes, which are sterile, will be released into the environment where they will mate. Eventually, the population of the Aedes mosquitoes in the area would drop, substantially enough that it will fall below the disease transmission threshold.

Dr Ramachandran said the purpose-built field house at the Institute for Medical Research (IMR) was the most advanced (near-field) tests of a RIDL (Release of Insects carrying a Dominant Lethal) mosquito strain conducted, worldwide.

But field tests are necessary to test the effectiveness of the RIDL plan.

"We need to have an island or a place rather than the laboratory-scale rearing to judge effectiveness.

"We also need to educate the public on the importance of this biotechnological solution."

He assured everyone that there was absolutely no question of the mosquitoes endangering the people.

The fact is the RIDL mosquito is male, and therefore doesn't bite. Second, the RIDL male is sterile and cannot father a "monster" mosquito or any mosquito for that matter.

Previously, biotechnology warfare saw the mass release of male mosquitoes sterilised by radiation (sterile insect technique) to control or eliminate several major agricultural pests.

However, radiation weakened the male mosquitoes to the extent that they were unable to compete successfully for mates, and so unable to curb the problem.

Dr Ramachandran said the RIDL technology, however, overcame this hitch.

"Studies conducted at IMR indicated that the basic life cycle and growth rate of the genetically transformed Aedes aegypti was not affected by the genetic manipulation, which is important for the successful implementation of this technology," he told the New Straits Times.

Dr Ramachandran added that the pilot project would be conducted under proper management, containment and surveillance.

Not enough Aedes mosquitoes, would ultimately mean no dengue.

THERE IS 'NOTHING TO FEAR'

Q: What is a genetically modified mosquito?
A: There have been many attempts to make mosquitoes unable to transmit dengue (or malaria, or other diseases). Such methods would require the genetically-modified (GM) mosquitoes to establish stable, permanent, breeding populations in the wild.

No such strains have actually been developed, and Oxitec's approach is different. We aim to develop genetically sterile mosquitoes that will mate with wild females but have no viable progeny (offspring), thereby suppressing the target population.

Q: Is it safe to release GM mosquitoes?
A: Yes. All available evidence and analysis indicate that it is safe to release Oxitec's strain. However, this assertion is based on a great deal of work and analysis.

Bear in mind that the purpose is to control dengue, a major disease with 100 million cases per year worldwide.

Therefore, in assessing the risks of any technology, consideration of the consequences of not using or testing the technology should also be made.

At present, that cost is 100 million cases of dengue per year, with about 100,000 deaths.

Q: Have similar experiments been carried out before?
A: There are several related experiments. One trial using sterile mosquitoes was conducted in El Salvador in the 1970s, where 4.4 million sterile mosquitoes were released in a 15 square km area over 22 weeks.

This successfully eliminated the target mosquito population. They then went on to a much larger area, and were able to suppress the population but not quite eliminate it.

The reason was the migration of mosquitoes into the area. The need to avoid such immigration, especially for a small trial experiment, is the primary reason for needing a reasonably isolated site, such as an island.

Another example is the pink bollworm (Pectinophora gossypiella), a moth that is a pest of cotton. Working with the US Department of Agriculture, Oxitec's GM insects have been used in two years of open-field trials, so far releasing around 1.2 million GM moths.

These trials have gone very well and Oxitec's strain has performed exactly as predicted.

There were no negative outcome of any type (whether environmental, agricultural or to human health) detected.

Naturally, these trials were subject to rigorous evaluation by the US regulatory authorities before any releases occurred.

Q: How were the mosquitoes sterilised?
A: In the El Salvador case, the mosquitoes were sterilised chemically. These chemicals were toxic, and would probably not be permitted today.

Q: What are some of the benefits of using Oxitec's mosquitoes?
A: There's no use of toxic chemicals in the environment, minimal off-target effects as the insects released will mate only with insects of their own species, and, unlike sprays and other control methods, insects cannot "hide" from Oxitec's mosquitoes as insects need to find mates for their own reproductive success.

Q: Once the GM mosquitoes have mated with the female Aedes mosquitoes, what happens to them. Do they just die off?
A: Aedes is a relatively short-lived species: males live around 10 days or so in the wild. In the laboratory, under ideal conditions, they can live a bit longer, perhaps a month. Mating does not kill them. Male mosquitoes will go on to look for more mates.

Q: It has been reported that such methods are a breakthrough and has never been done before. So is Oxitec or the Malaysian Institute of Medical Research the brains behind this project?
A: Both Oxitec and the IMR take pride in developing this breakthrough technology.

Oxitec invented and developed the technology in the laboratory. The IMR will be the first to develop this approach for practical use.

Q: Is it safe to release millions of GM mosquitoes in one area (Pulau Ketam) which is occupied by thousands of people. Will this experience harm their livelihood in anyway? What is the guarantee?
A: I can't speak specifically about any particular site, but leaving that aside, the answer is yes, it is safe.
- Safe to humans: only female mosquitoes bite; we will remove females before release. In all relevant aspects other than sterility, our mosquitoes are equivalent to other mosquitoes -- non-toxic to anything that eats them.
- The purpose of releasing the sterile mosquitoes is to control the wild mosquito population and so reduce biting and hence disease transmission.
- Harm to livelihood. The trial will have no impact on the livelihood of the population apart from the benefit of reducing the days they are unable to work because of sickness, or their children absent from school.

It will also not have an effect on environmental safety or on livelihood, such as fishing and agriculture, as no insecticides or toxic chemicals are used.

Q: Several environmentalists and politicians are against this approach, claiming that it can affect the ecosystem and a negative impact.
A: Many people will have legitimate concerns, much of this by analogy with the controversy over GM crops.

Q: Have tests been done by Oxitec to prove that its GM mosquitoes are no threat to the environment?
A: Oxitec does extensive testing to make sure that the mosquitoes are only different from the wild ones in their ability to reproduce. For predators, these mosquitoes are identical to the wild ones.

Q: One environmentalist in Malaysia feared that GM mosquitos may mutate or mate with other insects once its tasks of mating with the female Aedes mosquitoes is done. Is this fear real?
A: No. I think this concern about interbreeding with other insects arises from a genuine issue with some GM crops.

Many crop plants have native relatives with which they can interbreed, and this provides a route by which the introduced genes in a GM plant can "escape" into the environment.

However, this does not apply to Oxitec's GM mosquitoes, for two reasons: mosquitoes are not capable of interbreeding with other insect species, and, Oxitec is not adding beneficial genes to the mosquito, rather we are adding genes that will sterilise or kill the mosquito.

Such genes do not confer a selective advantage but quite the opposite.

Therefore, such genes will rapidly be lost, rather than spread.

Q: How about antibiotic and insecticide resistance?
A: Oxitec does not use antibiotic-resistant genes or insecticide-resistant genes.

Q: Is this the best way (GM mosquitoes) to eradicate the dengue epidemic?
A: Current methods for controlling dengue are clearly inadequate. There are no vaccines or specific therapeutic drugs, so controlling the mosquito is the only option.

Oxitec's technology is the first such method in a long time.

It should be tested -- in an appropriate, careful, rigorous, stepwise manner.