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.

New Recommendations For Screening And Testing Newborn Children

New recommendations on testing and screening newborn children for genetic diseases have been published in the latest policy statements of the American Academy of Pediatrics (AAP) and The American College of Medical Genetics and Genomics (ACMG).
They believe that it is necessary to test all newborn children as it is in the best interest of their health, showing their support for mandatory genetic testing and screening.

Millions of newborns undergo genetic screening every year.

However, additional genetic testing after the initial screening is far less common.

Most additional genetic testing conducted after the newborn period is mainly carried out on children who show signs and symptoms of intellectual disability for diagnostic purposes.

Beyond the initial screening, the decision to carry out additional testing should rest on the parents, say the experts.

There were distinct differences between the recommendations for testing for childhood-onset conditions and testing for conditions that appear in adulthood. The experts encouraged testing children who are at risk of childhood-onset conditions, but discouraged testing for diseases or conditions that appear later in adulthood.

They also noted that when a child shows early symptoms of a disease, it is necessary to make a quick diagnosis and evaluate the best courses of action, guiding the family in making a decision for the best of the child.

In fact, according to a previous study published in the journal Pediatrics, the majority of parents would accept and embrace predictive genetic testing for their children if offered.

Even though these two reports discourage testing for adult-onset conditions, some experts believe that results concerning these conditions could help adjust lifestyle risks early on.

One of the policy authors, Dr. Lainie Friedman Ross, said:

"There is an important role for counseling before and after genetic screening. The focus should be on education of families, counseling them and helping them make decisions that focus on the child's best interest.

Clearly, if a child has symptoms, we need a diagnosis to help the family make clinical decisions that are in the child's best interest. This is important even when the disease has no current therapies."

Sometimes genetic testing can give incorrect results or interpretations; the ACMG suggests that a person who is certified in either Clinical Molecular Genetics (ABMG) or Molecular Genetic Pathology (ABPath/ABMG) should always review test results.

In addition, they state that pre- and post-test counseling should be provided to patients by an ABMG certified Clinical Geneticist or ABGC/ABMG certified Genetic Counselor.

In view of the rapid advances made in genetics and genomics, the authors stress that health care providers and pediatricians should always be informed on what the best new practices are.