Mosquitoes With Altered Smell Gene Lose Preference For Humans

By changing one gene, scientists have bred a mosquito that does not seek out the smell of humans in preference to other animals. The team behind one of the first successful attempts to genetically engineer mosquitoes believes their work not only shows what can be done with the latest genetic techniques, but also helps us better understand the insect's attraction to humans and therefore how to block it.
Lead researcher Leslie Vosshall, a Howard Hughes Medical Institute (HHMI) investigator at The Rockefeller University in New York, says in a statement:

"The time has come now to do genetics in these important disease-vector insects. I think our new work is a great example that you can do it."

"By disrupting a single gene, we can fundamentally confuse the mosquito from its task of seeking humans," she adds.

Vosshall and colleagues write about their work in a paper published online in Nature on 29 May.

Their report follows another study published recently in PLOS ONE, where researchers from the London School of Hygiene & Tropical Medicine in the UK describe how malaria-carrying mosquitoes are more strongly attracted to the smell of humans.

Starting Point Was a Gene in Flies

After scientists in 2007 announced they had sequenced the complete genome of Aedes aegypti, the mosquito that carries dengue and yellow fever, Vosshall switched her lab's focus from Drosophila flies to mosquitoes and set about trying to alter their genes.

From working with genetically engineered flies, she and her team already knew of a gene called orco that was important for the fly's sense of smell. So, as Vosshall explains, they started working on this gene in mosquitoes:

" ... we had some hints that mosquitoes interact with smells in their environment, so it was a good bet that something would interact with orco in mosquitoes."

Genetic Engineering Tools

To mutate the orco gene in Aedes aegypti, the team used "zinc-finger nucleases" (ZFNs), powerful tools that can be designed to target and cleave specific sequences of genomic DNA.

First, they injected ZFNs into mosquito embryos and when these matured, they sought out mutant individuals and used them to generate mutant strains so they could study the behavior of the orco gene in mosquitoes.

They discovered that brain cells linked to sensing odors were not as active in the genetically engineered mosquitoes. But they also found some other interesting changes.

Less Preference for Human Odor

Normally, when presented with a choice between humans and other animals, non-mutant Aedes aegypti mosquitoes fly toward humans, attracted by their smell.

But when Vosshall and colleagues gave their mutant mosquitoes a choice between human scent and that of guinea pigs, they did not show a preference for humans. This was the case even in the presence of carbon dioxide, which is supposed to enhance the attraction of mosquito to humans.

It appears that changing a single gene, the orco gene, disrupts the mosquito's ability to seek human prey.

However, this experiment did not establish precisely how the mutated mosquito lost the preference for human smell.

For example, did the mutated insect lose its ability detect that the guinea pig smell is not a preferred one, or did it lose the ability to discriminate that the human smell is the one to go for? Or did the altered gene cause both these changes?

Response to DEET

In a second part of their study, Vosshall and colleagues found that the mosquitoes with orco mutations were attracted to human skin even when it was protected by the common insect repellant DEET.

They exposed them to two human arms: one slathered in a solution of 10% DEET, and the other untreated. The insects flew equally to both arms, showing therefore that they could not smell the DEET.

However, once the mutant mosquitoes landed on the arms, they quickly flew away from the one slathered in DEET solution.

Two Different Odor-Sensing Mechanisms Identified

The team concluded that their experiments with DEET on human arms showed the mosquitoes are using two separate mechanisms to sense the DEET.

"One is what's happening in the air, and the other only comes into action when the mosquito is touching the skin," Vosshall explains.

There has been talk of a dual mechanism, but this is the first experiment to show it.

Vosshall's team now wants to explore how the orco protein interacts with the mosquito's smell receptors to shape its sense of smell.

"We want to know what it is about these mosquitoes that makes them so specialized for humans," she says.

"And if we can also provide insights into how existing repellants are working, then we can start having some ideas about what a next-generation repellant would look like," she adds.

In another recently published study, US researchers suggest it may be possible to use a bacterium that stops malaria parasites developing in mosquitoes.

IPhone Microscope Helps Diagnose Intestinal Worms

smart phones are transforming the way that people communicate throughout the world. Now scientists are using them in an innovative way to help diagnose intestinal worm infections in school children living in rural Tanzania.

The scientists have developed an inexpensive microscope using a glass lens costing $8 USD, a strip of double-sided tape, and a cheap flashlight - altering an iPhone 4s into a device that can detect intestinal worm infections; parasites that infect two billion people and result in malnutrition.

Isaac Bogoch, MD, an infectious disease specialist at Toronto General Hospital and the study's lead author explained:

"There's been a lot of tinkering in the lab with mobile phone microscopes, but this is the first time the technology has been used in the field to diagnose intestinal parasites."

The scientists' findings were published in the American Journal of Tropical Medicine and Hygiene, and evaluated 199 stool samples of children using their unique device.

Along with a standard light microscope the researchers examined the samples with the cell phone microscopes and a regular laboratory slide. The kids participating in the trial on Pemba Island, Tanzania, were undergoing different treatments for eliminating intestinal worms.

Scientists first covered the slide in cellophane, then used the double-sided tape to attach it to the camera, lit it from underneath with the flashlight and finally took a picture.

The iPhone microscope was found to be not as sensitive as a light microscope, however, the scientists believe that with some changes it will come close. Bogoch commented, "We think cell phone microscopes could soon become a valuable diagnostic tool in poor, remote regions where intestinal worms are a serious health problem, particularly in children."

Intestinal Worms - A Global Issue

The cell phone microscope sensitivity was dependent on the type of worm and the strength of the infection.

Scientists have developed the camera on an iPhone into a microscope that can detect intestinal worm infections.
Photo Credit: Isaac Bogoch

For example, the cellphone found 81 percent of infections of giant roundworm (A. lumbricoides) and 54 percent of roundworm infections (T. trichiura ). But, it only detected 14 percent of all hookworm infections; the researchers say that this is due to the much smaller number of eggs present than with the other parasites.

"It was quite successful at detecting moderate to heavy infections, but not very good at detecting mild infections where there might be only a few eggs in the sample," Bogoch said.

Worms that infect the intestines, such as roundworms and hookworms - or soil-transmitted helminths - harm nearly two billion people worldwide. In isolated, poor regions of developing nations rates of this disease are particularly high and can result in chronic malnutrition and anemia in kids.

Bogoch and his team aimed to find an alternative tool by taping a 3 millimeter ball lens to the camera of Bogoch's Apple iPhone 4S - one he already owned. However, the researchers noted that any phone that has a camera with a zoom option could work effectively. Ball lenses are normally used in the telecommunications field in couplings for optical fiber cable. They are inexpensive - generally $8 to $10 USD.

Instead of an electric light, they used a small flashlight that just needs a single battery for many hours of operation. The entire set-up can be developed for $15 USD, in addition to the cost of the phone, and can be assembled in five minutes.

Cell Phone Microscope - Several Implications

The authors believe that the "mobile phone microscope would likely be of clinical use when it is sensitive enough to detect 80 percent of infections," and note that even now there are new developments underway to improve the current cell phone microscopes.

Bogoch said, "I'm confident that in the near future we will see cell phone microscopes widely used in low-resource settings. They're easy to make, portable, and today, you can find mobile phones with cameras even in some of the most remote regions in the world."

The cell microscope can be used for treating and diagnosing people with worm infections as well as observing the prevalence of disease amongst the broader population.

One example could be when administering drug treatment to large populations. Cell phone microscopes could serve as cheap and effective tools to calculate the effectiveness of these mass drug administration campaigns.

David H. Walker, MD, president of the American Society of Tropical Medicine and Hygiene said:

"I have nothing but praise for the ingenuity of scientists using all available tools to solve pressing health problems in some of the poorest parts of the world. This study is an illustration of how a modest investment in tropical disease research can help reap enormous health benefits for children."