Sunday November 21, 2010
Genetically-modified Aedes aegypti mosquitoes will soon be released in
Bentong and Alor Gajah in the first-ever field trial in Malaysia.
SOON, genetically-modified (GM) male Aedes aegypti mosquitoes will be buzzing around the districts of Bentong in Pahang and Alor Gajah in Malacca.
No, it is not a follow-up to the Cicakman (2006) movie, but the latest step in the Government’s efforts to control the transmission of the dengue virus.
This virus, which causes dengue fever, is transmitted solely by the bite of the female Aedes mosquito, and most commonly, those of the A. aegypti species.
The GM male mosquitoes are being released in a limited mark-release-recapture field trial designed to test their flying range and ability to survive in the wild.
The small-scale field trial marks the third stage of experiments on the mosquitoes by the Institute of Medical Research (IMR).
The institute has been working on the mosquitoes since 2006, in partnership with Oxitec Limited, a spin-off biotechnology company from the University of Oxford, United Kingdom. Oxitec owns the rights to the A. aegypti strain OX513A being tested.
A mosquito symbolising dengue fever displayed on a pickup truck
during a health campaign by medical personnel in Phnom Penh, Cambodia. Dengue
cases are increasing all over the world, and Asean countries are particularly
affected. — A P
For the past few years, IMR has conducted laboratory tests on the mosquitoes, as well as observed them in a fully contained trial facility, which simulated the living space of an urban household of two to four people.
According to IMR’s application for approval to the National Biosafety Board (NBB), the results of their previous experiments have shown that there are no significant differences between the GM mosquitoes and normal A. aegypti mosquitoes in terms of the egg, larval, and pupal stages, and their reproductive abilities.
The only significant difference between the two types of mosquitoes was in the number of days they survived as adults, with the normal types outliving the GM mosquitoes by an average of six days.
This means that once the GM mosquitoes have been bred to adulthood, they generally live, reproduce, and die just like their wild counterparts. The difference lies in the fate of their offspring.
How it will work
The adult A. aegypti male mosquitoes have been genetically modified to include two new traits: fluorescence and conditional lethality.
The fluorescence trait simply allows those mosquitoes carrying the “extra” genes to be easily identified as they will “light up” or fluorescence when a light of a certain wavelength is shone on them. (Think how the various CSI investigators use ultra-violet lights to check for semen stains.)
The conditional lethality trait is the characteristic of main interest. IMR’s application states that this trait causes the normal cell cycle of the mosquito to be suppressed in the absence of the antibiotic tetracycline.
NBB’s Genetic Modification Advisory Committee (GMAC) chairman Dr Ahmad Parveez Ghulam Kadir told Fit4Life that what happens is that the gene causes the production of a certain enzyme that reacts with tetracycline in the GM mosquito.
In the absence of the antibiotic, the enzyme builds up to toxic levels and causes the mosquito to die young.
This means that any mosquito born with this gene will die at the late larval or pupal stage of their lives as long as they do not come into contact with tetracycline. (See GM A. aegypti life cycle)
So, once the GM male mosquito mates with a normal female A. aegypti mosquito and reproduces, any offspring they have will not survive to adulthood.
The Cayman Islands in the Carribbean recently concluded a six-month suppression field trial involving the same GM A. aegypti mosquito strain to see if they could lower the population of the A. aegypti mosquitoes in the tested area.
Around three million GM male mosquitoes were released into a 16-hectare area over the months of June to October.
The results, which were announced at a press briefing in London last week, showed that the A. aegpyti population in the area was reduced by about 80%.
Oxitec chief science officer Dr Luke Alphey, who was present at the briefing, said that the results were influenced by migration of mosquitoes from an adjacent area into the tested area.
“Estimates suggest that in many places, 80% suppression (of the A. aegypti population) would actually be sufficient (to control the transmission of dengue).
“We would expect to do much better than that if we were in an area that was not immediately adjacent to an area heavily infested with mosquitoes. In a larger trial, if we were doing a whole town, for example, then we would expect to get much better than 80% suppression,” he said.
In response to a query on how many GM male mosquitoes would have to be released in order to control the transmission of dengue, Dr Alphey said: “In an urban environment, we would expect to have to release in the general range of 20 sterile male mosquitoes per human inhabitant per week.
“And the outcome in a large-scale programme would be suppression to an effectively zero level.”
Where we are
Malaysia is only one step behind the Cayman Islands in terms of testing the GM mosquitoes. The current planned field trial is a preparatory step to a larger scale suppression field trial, assuming that all goes well.
At a press conference announcing the decision of the NBB to approve IMR’s application last month, Dr Parweez said: “We are entering Phase One. Cayman is already in Phase Two – testing the effects on the progeny (of the GM male mosquitoes and normal female mosquitoes in the wild).
“If IMR wants to enter Phase Two, we will have to sit down again to review the application.”
Natural Resources and Environment Ministry Biosafety director-general Letchumanan Ramatha, who was also present at the press conference, said that both the NBB and GMAC had referred to the Cartagena Protocol on Biosafety to the Convention on Biological Diversity in making their decision.
The Protocol, which Malaysia has ratified, is an international treaty governing the movements of living modified organisms resulting from modern biotechnology from one country to another.
It seeks to protect biological diversity from the potential risks posed by these modified organisms.
Dr Parweez said: “We have considered all the various possibilities of releasing these mosquitoes, and we have found that there is very low or negligible risk.”
He said that after their own research and gathering views from the public, including non-governmental organisations and scientists, GMAC only had two potential areas of concern.
“The first of these is that there is a 3% survivability of the GM larvae in the lab. And secondly is the risk of releasing female GM mosquitoes along with the males.”
However, the committee believes that even if some of the GM larvae survive to adulthood, they will die a natural death within the normal two-to-four-week lifespan of the adult A. aegypti mosquitoes, as shown in the laboratory tests by the IMR.
In addition, the field trial will involve the setting up of traps at various locations to see the extent of the GM mosquitoes flight range, and extensive fogging and a gotong-royong will be carried out throughout the tested area after the trial is complete to ensure that all the adult A. aegypti mosquitoes are killed, and that any mosquito breeding grounds are eradicated. (Refer to Compulsory conditions)
On the risk of releasing female GM mosquitoes, Dr Parweez said that GMAC had set the condition that not only should the pupaes of the mosquitoes to be released be mechanically sorted, but each pupae must also be manually rechecked by a team of three highly-trained IMR laboratory technicians.
The difference between the male and female A. aegypti mosquitoes is that the male mosquitoes do not bite humans and do not carry the dengue virus.
What will happen
A total of 4,000 to 6,000 GM male mosquitoes, along with an equal number of normal male mosquitoes, are expected to be released at Bentong and Alor Gajah respectively in the upcoming IMR field trial.
According to IMR’s application, each location will have two release phases.
The first phase will be a release at an uninhabited site around 0.5-1km away from the nearest human population, while the second phase will be at an inhabited site. The areas of the site can be up to five square kilometres. The releases will be carried out from a single point, and may be done over two consecutive days or just one day. The trials may be repeated.
According to an officer in the Bentong Municipal Council, the council had given the approval for the trial to go ahead in a meeting last week.
“We gave them (IMR) the go-ahead to release the mosquitoes any time within the next three months, so it will depend on the weather,” he said.
The officer, who declined to be named as he was not authorised to speak to the media, added that it would be up to IMR to inform the public about the release through the media.
Meanwhile, an officer in the Alor Gajah Municipal Council, who also declined to be named, said that he had not heard of any planned release of the GM mosquitoes in his district as yet.
A request to interview the IMR scientists involved was turned down.
If the GM male mosquitoes are successful in bringing down the population of A. aegypti mosquitoes, they will be one additional weapon in the arsenal against dengue.
Dr Alphey does not believe that his company’s GM mosquitoes will be the silver bullet that kills off dengue, but he does believe that they will help reduce the transmission of the disease significantly.
SOON, genetically-modified (GM) male Aedes aegypti mosquitoes will be buzzing around the districts of Bentong in Pahang and Alor Gajah in Malacca.
No, it is not a follow-up to the Cicakman (2006) movie, but the latest step in the Government’s efforts to control the transmission of the dengue virus.
This virus, which causes dengue fever, is transmitted solely by the bite of the female Aedes mosquito, and most commonly, those of the A. aegypti species.
The GM male mosquitoes are being released in a limited mark-release-recapture field trial designed to test their flying range and ability to survive in the wild.
The small-scale field trial marks the third stage of experiments on the mosquitoes by the Institute of Medical Research (IMR).
The institute has been working on the mosquitoes since 2006, in partnership with Oxitec Limited, a spin-off biotechnology company from the University of Oxford, United Kingdom. Oxitec owns the rights to the A. aegypti strain OX513A being tested.
A mosquito symbolising dengue fever displayed on a pickup truck
during a health campaign by medical personnel in Phnom Penh, Cambodia. Dengue
cases are increasing all over the world, and Asean countries are particularly
affected. — A P For the past few years, IMR has conducted laboratory tests on the mosquitoes, as well as observed them in a fully contained trial facility, which simulated the living space of an urban household of two to four people.
According to IMR’s application for approval to the National Biosafety Board (NBB), the results of their previous experiments have shown that there are no significant differences between the GM mosquitoes and normal A. aegypti mosquitoes in terms of the egg, larval, and pupal stages, and their reproductive abilities.
The only significant difference between the two types of mosquitoes was in the number of days they survived as adults, with the normal types outliving the GM mosquitoes by an average of six days.
This means that once the GM mosquitoes have been bred to adulthood, they generally live, reproduce, and die just like their wild counterparts. The difference lies in the fate of their offspring.
How it will work
The adult A. aegypti male mosquitoes have been genetically modified to include two new traits: fluorescence and conditional lethality.
The fluorescence trait simply allows those mosquitoes carrying the “extra” genes to be easily identified as they will “light up” or fluorescence when a light of a certain wavelength is shone on them. (Think how the various CSI investigators use ultra-violet lights to check for semen stains.)
The conditional lethality trait is the characteristic of main interest. IMR’s application states that this trait causes the normal cell cycle of the mosquito to be suppressed in the absence of the antibiotic tetracycline.
NBB’s Genetic Modification Advisory Committee (GMAC) chairman Dr Ahmad Parveez Ghulam Kadir told Fit4Life that what happens is that the gene causes the production of a certain enzyme that reacts with tetracycline in the GM mosquito.
In the absence of the antibiotic, the enzyme builds up to toxic levels and causes the mosquito to die young.
This means that any mosquito born with this gene will die at the late larval or pupal stage of their lives as long as they do not come into contact with tetracycline. (See GM A. aegypti life cycle)
So, once the GM male mosquito mates with a normal female A. aegypti mosquito and reproduces, any offspring they have will not survive to adulthood.
The Cayman Islands in the Carribbean recently concluded a six-month suppression field trial involving the same GM A. aegypti mosquito strain to see if they could lower the population of the A. aegypti mosquitoes in the tested area.
Around three million GM male mosquitoes were released into a 16-hectare area over the months of June to October.
The results, which were announced at a press briefing in London last week, showed that the A. aegpyti population in the area was reduced by about 80%.
Oxitec chief science officer Dr Luke Alphey, who was present at the briefing, said that the results were influenced by migration of mosquitoes from an adjacent area into the tested area.
“Estimates suggest that in many places, 80% suppression (of the A. aegypti population) would actually be sufficient (to control the transmission of dengue).
“We would expect to do much better than that if we were in an area that was not immediately adjacent to an area heavily infested with mosquitoes. In a larger trial, if we were doing a whole town, for example, then we would expect to get much better than 80% suppression,” he said.
In response to a query on how many GM male mosquitoes would have to be released in order to control the transmission of dengue, Dr Alphey said: “In an urban environment, we would expect to have to release in the general range of 20 sterile male mosquitoes per human inhabitant per week.
“And the outcome in a large-scale programme would be suppression to an effectively zero level.”
Where we are
Malaysia is only one step behind the Cayman Islands in terms of testing the GM mosquitoes. The current planned field trial is a preparatory step to a larger scale suppression field trial, assuming that all goes well.
At a press conference announcing the decision of the NBB to approve IMR’s application last month, Dr Parweez said: “We are entering Phase One. Cayman is already in Phase Two – testing the effects on the progeny (of the GM male mosquitoes and normal female mosquitoes in the wild).
“If IMR wants to enter Phase Two, we will have to sit down again to review the application.”
Natural Resources and Environment Ministry Biosafety director-general Letchumanan Ramatha, who was also present at the press conference, said that both the NBB and GMAC had referred to the Cartagena Protocol on Biosafety to the Convention on Biological Diversity in making their decision.
The Protocol, which Malaysia has ratified, is an international treaty governing the movements of living modified organisms resulting from modern biotechnology from one country to another.
It seeks to protect biological diversity from the potential risks posed by these modified organisms.
Dr Parweez said: “We have considered all the various possibilities of releasing these mosquitoes, and we have found that there is very low or negligible risk.”
He said that after their own research and gathering views from the public, including non-governmental organisations and scientists, GMAC only had two potential areas of concern.
“The first of these is that there is a 3% survivability of the GM larvae in the lab. And secondly is the risk of releasing female GM mosquitoes along with the males.”
However, the committee believes that even if some of the GM larvae survive to adulthood, they will die a natural death within the normal two-to-four-week lifespan of the adult A. aegypti mosquitoes, as shown in the laboratory tests by the IMR.
In addition, the field trial will involve the setting up of traps at various locations to see the extent of the GM mosquitoes flight range, and extensive fogging and a gotong-royong will be carried out throughout the tested area after the trial is complete to ensure that all the adult A. aegypti mosquitoes are killed, and that any mosquito breeding grounds are eradicated. (Refer to Compulsory conditions)
On the risk of releasing female GM mosquitoes, Dr Parweez said that GMAC had set the condition that not only should the pupaes of the mosquitoes to be released be mechanically sorted, but each pupae must also be manually rechecked by a team of three highly-trained IMR laboratory technicians.
The difference between the male and female A. aegypti mosquitoes is that the male mosquitoes do not bite humans and do not carry the dengue virus.
What will happen
A total of 4,000 to 6,000 GM male mosquitoes, along with an equal number of normal male mosquitoes, are expected to be released at Bentong and Alor Gajah respectively in the upcoming IMR field trial.
According to IMR’s application, each location will have two release phases.
The first phase will be a release at an uninhabited site around 0.5-1km away from the nearest human population, while the second phase will be at an inhabited site. The areas of the site can be up to five square kilometres. The releases will be carried out from a single point, and may be done over two consecutive days or just one day. The trials may be repeated.
According to an officer in the Bentong Municipal Council, the council had given the approval for the trial to go ahead in a meeting last week.
“We gave them (IMR) the go-ahead to release the mosquitoes any time within the next three months, so it will depend on the weather,” he said.
The officer, who declined to be named as he was not authorised to speak to the media, added that it would be up to IMR to inform the public about the release through the media.
Meanwhile, an officer in the Alor Gajah Municipal Council, who also declined to be named, said that he had not heard of any planned release of the GM mosquitoes in his district as yet.
A request to interview the IMR scientists involved was turned down.
If the GM male mosquitoes are successful in bringing down the population of A. aegypti mosquitoes, they will be one additional weapon in the arsenal against dengue.
Dr Alphey does not believe that his company’s GM mosquitoes will be the silver bullet that kills off dengue, but he does believe that they will help reduce the transmission of the disease significantly.
http://thestar.com.my/health/story.asp?file=/2010/11/21/health/7435187&sec=health
