Sterilizing Mosquitoes to Fight Malaria

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QUESTION

Is it possible to breed mosquitoes in the laboratory and then sterilize them and release them into the environment in order to reduce their rate of reproducing.

ANSWER

That is a very good question, and indeed efforts to genetically modify mosquitoes in order to control the various diseases they transmit are underway in many laboratories across the world.

For almost 15 years, scientists have had the ability to modify mosquitoes so that they are sterile. The aim, as you rightly describe, is then to release these sterile mosquitoes into the wild in order to reduce numbers. If the gene that causes sterility can be passed to future offspring, without any reduction in survival of the insect, then the eventual result will be a total population extinction.

To date, many of the major mosquito disease vector species have been successfully genetically modified, though there are many fewer instances of field testing of these modified insects. For example, in 2000/2001, a World Health Organisation-led project in India created sterile mosquitoes of one species of each of the three main disease vector genera: Culex, Aedes and Anopheles, the latter of which acts as vectors for malaria. However, the project did not, in the end, release any of the modified Anopheles vectors into the wild.

While many scientists applaud the benefits of this approach (such as being very species-specific and being more environmentally friendly than spraying), there are also causes for caution. For example, there are concerns that the loss of mosquitoes in the food chain will have a negative impact on animals that rely on them for food. Similarly, if mosquitoes vanish from an ecosystem, their “niche” may be filled by another organism that is equally or even more dangerous and destructive, such as a crop pest or another disease vector. There is also a worry that changing mosquitoes may have unexpected and dangerous effects on the disease itself, for example forcing it to evolve into a more severe disease or changing its epidemiological patterns in ways we cannot predict in advance.

Finally, not all scientists are convinced that the approach will work in the first place—the sterile mosquitoes will have to survive equally well or better than normal mosquitoes in order to establish in the population, and must be equally or more successful at reproducing. As such, while a lot of money is being poured into GM mosquitoes, it is still the center of vigorous debate.

Perhaps the best indication of this controversy came last year, when Oxitec, a British company, released sterile Aedes aegypti mosquitoes on the Cayman Islands. These mosquitoes are the vectors of dengue fever, and so all eyes are on this study to see whether indeed sterile mosquitoes can survive in a population, and if they do, what other effects they will have longer term on the population size of mosquitoes and the rest of the ecosystem. You can read more information about that here: Oxitec: GM Mosquito Factory.

Mosquitos Make Proteins to Handle Heat Spike of Hot Blood Meals

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Mosquitoes make proteins to help them handle the stressful spike in body temperature that’s prompted by their hot blood meals, a new study has found.

The mosquito’s eating pattern is inherently risky: Taking a blood meal involves finding warm-blooded hosts, avoiding detection, penetrating tough skin and evading any host immune response, not to mention the slap of a human hand.

Until now, the stress of the hot blood meal itself has been overlooked, researchers say.

Scientists have determined in female mosquitoes that the insects protect themselves from the stress of the change in body temperature during and after a meal by producing heat shock proteins. These proteins protect the integrity of other proteins and enzymes, in turn helping the mosquitoes digest the blood meal and maintain their ability to produce eggs.

Tests in two other types of mosquitoes and in bed bugs showed that these insects undergo a similar response after a blood meal.

“These heat shock proteins are really important in a lot of stress responses. Our own bodies make these proteins when we have a fever,” said David Denlinger, professor of evolution, ecology and organismal biology at Ohio State University and senior author of the study. “It’s one of those things that, in retrospect, seems obvious – that blood meals might cause a stress like that. But it hadn’t been pursued before.”

The research appears this week in the online early edition of the Proceedings of the National Academy of Sciences.

Denlinger and colleagues conducted experiments in the Aedes aegypti mosquito, which is a carrier of yellow fever.

The researchers placed sensors on female mosquitoes and observed that upon taking in a blood meal on a chicken, the insects’ body temperatures increased from 22 to 32 degrees Celsius (71.6 to 89.6 Fahrenheit) within one minute – among the most rapid body temperature increases ever recorded in a cold-blooded animal. After the feeding, their body temperatures decreased to room temperature within a few minutes.

In response to that blood feeding, the mosquitoes’ level of Hsp70 – heat shock protein 70 – increased nearly eightfold within one hour and remained at least twice as high as usual for 12 hours. The increase in these proteins was most pronounced in the midgut area.

Denlinger and colleagues tested potential triggers for this protein increase by injecting the mosquitoes with a saline solution at two temperatures: 37 degrees Celsius (98.6 degrees Fahrenheit) and room temperature. Only the warmer saline generated an increase in Hsp70, suggesting that the elevation in temperature associated with the meal, rather than the subsequent increase in body volume, is what causes the generation of those proteins.

Sometimes, mosquitoes feed on cold-blooded amphibians, which should not cause the same amount of stress. To test that theory, the researchers also gave mosquitoes a feeding opportunity on cooler blood, which failed to generate an increase in heat shock proteins.

And what happens if this protein is not produced? The researchers manipulated the mosquitoes’ RNA to figure that out.

When the scientists knocked down expression of the gene that encodes the heat shock protein, the amount of Hsp70 production was reduced by 75 percent. Under those circumstances, mosquitoes still ate a normal blood meal. But blood protein levels remained elevated for a longer period of time, suggesting that digestion of those proteins was impaired. In addition, egg production decreased by 25 percent when the heat shock protein was suppressed.

Heat shock proteins help maintain the three-dimensional integrity of enzymes and proteins when temperatures rise suddenly, and can target damaged proteins and enzymes for elimination, Denlinger said. “We think that in this case, they are important to maintaining the integrity of some critical enzymes and proteins involved in digestive processes. When we knock out those proteins, it impairs digestion a bit and as a result the mosquitoes don’t lay as many eggs,” he said.

The researchers observed similar body temperature increases and elevations in Hsp70 levels in three other insects: Culex pipiens and Anopheles gambiae, mosquitoes that are carriers of West Nile virus and malaria, respectively, and Cimex lectularius, the bed bug. Though new knowledge about the genetics of these insects, especially the mosquitoes, might someday inform attempts to kill them as a method of disease control, Denlinger said the primary contribution of this research is better understanding of how mosquitoes protect themselves in this novel way.

This work was supported by grants from the National Institutes of Health/National Institute of Allergy and Infectious Diseases and the National Science Foundation.

Co-authors include Joshua Benoit, a former Ohio State graduate student who is now a postdoctoral researcher at Yale University, and Giancarlo Lopez-Martinez, Kevin Patrick, Zachary Phillips and Tyler Krause of Ohio State’s Departments of Entomology and Evolution, Ecology and Organismal Biology. Lopez-Martinez is now at the University of Florida.

Source: Proceedings of the National Academy of Sciences, Ohio State University