Few living things are more universally reviled than mosquitoes. Their persistent buzzing on summer nights and the itchy irritation of their bite are dreaded all over the world. However, beneath these mild annoyances lies true danger. Transmitters of yellow fever, malaria, dengue fever, Zika, and many other diseases, these insects are the deadliest animals in the world. Efforts to combat mosquito-borne diseases have ranged from vaccines against viral infections to insecticides intended to shrink mosquito populations, but none have proved a sufficient defense against this threat. But what if the menacing mosquitoes themselves could help vanquish the illnesses they spread? Rather than viewing them as mere agents in disease outbreaks, scientists now understand that mosquitoes can be a tool in preventing diseases from reaching humans in the first place. Genetic engineering holds the key for turning mosquitoes into our allies against a problem that has plagued humanity for centuries.
Diseases are transmitted from mosquitoes to humans when an infected pest bites someone, passing along pathogens such as viruses, bacteria, and parasites. These disease-causing agents infiltrate the human body, often resulting in serious or even fatal illness. Even if only a few mosquitoes in a large population originally carry pathogens, outbreaks of disease can still easily occur. This is because uninfected mosquitoes can also contract pathogens from their human prey; if a handful of people get infected by a single mosquito, each of them can transmit disease-causing agents to many other mosquitoes, which will then go on to infect more people.
Fighting the spread of these diseases is extremely challenging. Avoiding all contact with mosquitoes is infeasible, as these animals are widespread and numerous. Vaccinating against viral mosquito diseases is often a temporary fix, as virus populations quickly adapt to the defenses the vaccines confer. A new vaccine would have to be developed to combat each adapted version of the virus in order to keep up. Even the brute-force approach of trying to kill mosquitoes to limit the number of disease transmitters has produced only short-lasting results, as these organisms rapidly developed resistance to insecticides.
With traditional means of pest control found insufficient, scientists had to think outside the box. Was there a way to use the mosquitoes’ own adaptability against them? Enter genetic engineering.
An organism’s physical traits are largely determined by their genetic makeup. Each gene is composed of a sequence of biological molecules; the order and type of these molecules confers a specific trait, such as brown eyes. Genetic engineering is the process of editing a gene sequence to change something specific about the organism. Currently, scientists most commonly make these edits using a system called CRISPR/Cas9. This involves two molecules that work together: one that sticks to a specific gene of interest and another that follows it and cuts this gene sequence. The resulting changes can range from a single swap in the biological molecule sequence of a gene to deletions or insertions of large chunks of genetic material. The molecular tools needed to edit genetic sequences exist naturally in bacteria; the scientists who discovered how humans could use these tools, Emmanuelle Charpentier and Jennifer Doudna, were rewarded with a Nobel Prize in Chemistry.
This biological research breakthrough opened the door for a new approach in the fight against mosquito-borne illnesses. Lifespan and the ability to spread disease are among the traits that can be altered using genetic engineering to render mosquitoes a less potent foe. First undertaken by biotechnology company Oxitec in the 2000s, this idea is currently emerging as a leading defense against this global health hazard.
Oxitec’s most recent innovation targets the mosquito species Aedes aegypti, which thrives around the world in climates ranging from tropical to temperate and transmits a multitude of diseases. Where insecticides were failing, scientists aimed to use genetic engineering to cull mosquito populations. They started by inserting sequences into mosquito genes that result in the production of lethal toxins within the mosquito body. While such an edit certainly proves effective at killing, it can not be spread in wild populations because all altered mosquitoes die before producing offspring. Thus, scientists had to develop a way for some mosquitoes to carry and pass on the edits without dying from them. Fortunately, not all of these mosquitoes are dangerous; only female mosquitoes bite, while the males, which do not produce eggs and therefore do not need to obtain nutrients from blood, pose no threat to humans. Following this logic, scientists designed genetic edits that can be carried harmlessly by adult male mosquitoes, but are lethal in females, causing them to die shortly after hatching. This was accomplished by leveraging natural differences between the importance of certain genes in males and females. Placing the lethal edits in genes that are vital to the health of female bodies, but not male ones ensured that the latter would survive to spread the engineered gene in wild mosquito populations.5
Following testing to ensure these genetically modified organisms posed no threat to humans or the environment, they were released into the wild. While the females died by design, the affected males matured and mated with wild females, spreading their engineered genes. Once again, the female offspring died before reaching adulthood, decreasing the mosquito population. Since 2019, over one billion of these engineered mosquitoes have been released across parts of Brazil, the Cayman Islands, Panama, India, and the United States. While data collection is ongoing, a 2022 study found that the release of these genetically engineered mosquitoes reduced pest populations by over ninety percent in some parts of Brazil, successfully decreasing mosquito-borne disease transmission. Notably, because other species of mosquito that don’t transmit disease share habitats with Aedes aegypti, the elimination of these dangerous insects does not pose a threat to ecosystem stability, especially given that they are invasive in many parts of the world. Animals that rely on mosquitoes for food and plants that are pollinated by them will still have their needs met by the remaining mosquito species.
In 2022, a research team at Imperial College London took a different genetic engineering approach, this time focusing specifically on the mosquitoes responsible for spreading malaria, Anopheles gambiae. Malaria is one of the most devastating human diseases worldwide, with an estimated 263 million cases and 597,000 deaths in 2023. Children under five years old in sub-Saharan Africa face the highest risk of death from this disease. In order to pass from an infected mosquito to humans, the malaria-causing parasite must first develop in the insect’s gut before travelling to its salivary glands, where it is transmissible via bite. With adult mosquito lifespans typically lasting for only a couple of weeks, ninety percent of mosquitoes in nature will die before the malaria pathogens have matured enough to be contagious to humans.2 However, with mosquito populations reaching hundreds of thousands of insects, even this longest-living ten percent pose a massive global health threat.
In an attempt to further limit the number of mosquitoes capable of transmitting malaria, scientists genetically engineered these insects to produce antimicrobial molecules in their gut that attack the parasite responsible for causing malaria in humans. These molecules exist naturally in African clawed frogs and European honeybees; genetic engineering makes it possible to copy the genetic sequences directing their production and insert them into mosquito genes. This is just one example of the incredible power of nature to facilitate new technology, demonstrating the importance of protecting biodiversity for the good of wildlife and human society alike.
Inside the mosquito gut, the antimicrobial molecules interfere with the parasite’s ability to convert nutrients into energy, delaying their development by several days (Figure 1). Additionally, edited mosquitoes will have shorter lifespans because the production of the molecules requires energy that could otherwise be dedicated toward survival processes. Together, these impacts mean that fewer malaria-causing parasites are mature enough to be transmitted before their mosquito hosts die.
Figure 1: Genetic edits in mosquitoes can interfere with the development of malaria-causing parasites in their gut, preventing the disease from spreading to humans.
In these two cases alone, genetic engineering has been shown to combat mosquito disease transmission on two fronts: reducing the mosquito population size and making mosquitoes incapable of spreading disease. However, this work is far from over. Both approaches have limitations. Currently, genetically engineered mosquitoes must be constantly re-released into wild populations.2, 5 Otherwise, because these organisms produce fewer offspring than their wild counterparts—either due to the female offspring dying or shortened lifespan of the edited mosquitoes—the proportion of mosquitoes carrying the edits decreases over time. Eventually, the edits will disappear from the population.
A potential solution to this is incorporating gene drive techniques into the engineered organisms. In mosquitoes, humans, and many other organisms, individuals have two copies of every gene, one inherited from each parent. Naturally, each copy has a fifty percent chance of being passed from parent to offspring. When gene drive is used with engineered traits, these odds are disrupted, and the desired edited gene is given a much higher chance of being inherited. This can be done by inserting both the engineered gene and sequences for producing gene-editing molecules into the mosquito. When these are passed along to an offspring, the editing molecules make a cut in the other, unedited copy of the gene inherited from the wild parent. Natural mechanisms that repair genetic damage use the edited copy as a reference for what the cut sequence should be. This results in two copies of the edited gene in all offspring of the engineered mosquito. When these insects have offspring of their own, the gene drive process repeats and the engineered gene continues to be passed down for generations (Figure 2).
This work is already in progress, as the malaria-related edits were designed to be compatible with gene drive, but further testing is required to ensure there are no unintended consequences in nature.12 Additionally, both of the gene editing projects address only one species of mosquito each, leaving other disease-spreading mosquitoes unchecked. Finally, neither approach can aid against an ongoing disease outbreak. As such, it is vital that scientists, doctors, and governments continue working together to combine traditional efforts such as vaccination and mosquito nets with genetic engineering advancements to fight the threat of mosquito-borne diseases. But some day, with further research, mosquitoes will be reduced from a grave danger to humankind to a mere nuisance.
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