GM Mosquitoes:
Manipulating a corner of the ecosystem to halt the transmission of Malaria
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1897- Sir Ronald Ross discovered that mosquitoes transmit the malaria parasite.
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1960- first attempts to use sterile male mosquitoes to reduce wild populations.
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2002- The first GM Anopheles mosquito was created.
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2005- A useful technique for identifying a male GM mosquito was developed.
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2010- An Anopheles GM mosquito with increased Akt signaling was created.
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2011- A transgenic mosquito was created that expressed mouse antibodies against malaria.
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2011- A transgenic mosquito was created that was highly resistant to multiple microbes.
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2012- A twist on the approach: a mosquito carrying GM midgut bacteria was created.
Read more about these advancements below!
Technological Milestones !
Above- fluorescent microphotographs showing the transgenic expression of Beta2-EGPF at different developmental stages; the green fluorescence is only detected in males. This technology allows for efficient sorting of the males from the females. Such a sorting method could enable effecient mass production of male mosquitoes in the future, which could be used in a mosquito control method that utilizes delivery of sterile males to a population, or of males that carry a mutation lethal to offspring.
1897-
2005-
2002-
1960-
In Flordia 4.6 million sterile male mosquitoes were released to try to reduce the mosquito poplation. This proved unsuccessful, but was groundbreaking as it was the first attempt to try to modify the ecosystem using a modifieded organism (not GM just irradiated).
Sir Ronald Ross, born 1857, was a doctor, a scientist, and a poet. In 1897, while dissecting an Anopheles mosquito that had previously fed on a human patient with malaria, he found the malaria parasite in the mosquitoes' stomach tissue. Thus, Ross proved that the Anopheles mosquito was a vector of malaria parasite. This led to the institution of misquito control methods, saving millions of lives.
Ross recognized the massive importance his descovery; he wrote a poem about it on the very day he discovered the vector:
"This day relenting God
Hath placed within my hand
A wondrous thing: and God
Be praised. At his command
Seeking His secret deeds
With tears and toiling breath
I find thy cunning seeds,
O million-murdering Death.
I know this little thing
A myriad men will save.
O Death, where is thy sting,
They victory, O Grave!
Before Thy feet I fall,
Lord, who made high my fate;
For in the mighty small
Is shown the mighty great."
The first transgenic mosquito was produced at Johns Hopkins by Dr. Jacobs-Lorena and colleagues. The investigators expressed SM1 tetramer which inhibited the crossing of malaria parasited through the misquito salivary gland and midgut after a feeding. This misquito showed 80% inhibition of oocyte formation. Thus, the ability to transmit parasites was dramatically reduced in the GM misquitos (compared with controls). This study did not use the human malaria parasite but was tested with rodent models and rodent malaria parasites.
Andrea Crisani from London's Imperial College, inserted into misquitos a gene that glowed fluorescent green only in males. This was a milestone because it allowed researchers to seperate males from females on a large scale for sterile introductions or introduction of males that carry dominant lethal mutatuions (after mating with females, the result would be death of the genetic offspring).
Ross likely saw an image in his microscope similar to this. This image depicts oocysts (the spheres), malaria parasite developing, imbedded in the walls of a misquitoes' midgut.
2012
At Johns Hopkins, Dr. Jacobs-Lorena and colleagues created a GM bacterium from a microbe normally present in the midgut of Anopheles mosquitoes that secreted proteins toxic to the malaria parasite. This approach was noted to be easier than modifying the mosquito and was about 84% effective in eliminating the parasite.
2011-
At UC Irvine, Dr. Anthony James and his colleagues developed a transgenic Anopheles stephensi mosquito that expressed singed-chain antibodies derived from mouse monoclonal antibodies. These antibodies inhibited malaria parasites in the midgut and salivary gland. These mosquitoes had significantly lower infection levels than controls.
At Johns Hopkins, Dr. George Dimopoulos' lab created a transgenic Anopheles stephensi mosquito with enhanced immunity against Plasmodium (malaria parasites) and other microbial infections that is induced only after the blood meal. The transgene encodes a transcription factor in the midgut tissue.
2010-
In a colabrative effort between UC Davis and University of Arazona. The GM Misquitos created had increased Akt signaling. Overall it reduced the number of mosquitoes infected by 60-99%. The ones that were infected had a 75-99% reduced parasite load. The increased Akt signaling also caused an 18-20% decrease in the average lifespan of a mosquito. It is also important to note that the mosquitoes homozygous for this trait compleatly blocked the parasite.
In my opinion...This study has the advantage of developing resistance that is very specific to the malaria parasite rather than inhancing a more general immunity in the mosquito. Specific immunity is important because it potentially decreases the public concerns regarding the effects on the ecosystem.