Mosquito-borne diseases have plagued civilizations for millennia. Even today, malaria, dengue and yellow fever continue to constrain economic development in areas of Africa, Southeast Asia and South America where they are endemic. But compared with these enduring threats, acute outbreaks of illnesses such as Zika and chikungunya have gotten far more attention recently. Though the diseases themselves were first identified decades ago, the magnitude of their spread — facilitated by factors including higher population density, greater urbanization, globalization and the increased range of mosquitoes that carry them — is unprecedented. Acute disease outbreaks have occurred with greater frequency worldwide since 1980. At the same time, new incidences of vector-borne illnesses — those carried by one organism and transmitted to another — have cropped up as methods for detecting and tracking disease have improved. A recent bulletin from the Centers for Disease Control and Prevention (CDC), for example, reported a new case in Haiti of the Mayaro virus, which was first reported in Trinidad in 1954 but has been present in Haiti for at least two years.
On its own, the CDC's revelation does not portend a global crisis. Several factors determine the risk that an infectious disease presents to global economic activity, the criterion by which we measure an illness's geopolitical effect. These factors include ease of transmission, severity of symptoms, and whether an illness is endemic or epidemic. Endemic refers to the constant presence and/or usual prevalence of a disease or infectious agent in a population within a geographic area whereas an epidemic refers to a sudden outbreak in disease cases above what is expected in a given population and area. Relative to endemic diseases, which can hamper a country's economic growth and productivity for decades, outbreaks — especially of illnesses such as Zika and chikungunya, whose symptoms are mild — typically have less potential for long-term disruption. The recent Zika epidemic, in fact, has done little to interrupt international trade over the past few years, although the World Health Organization declared it a global health emergency. Still, outbreaks of these diseases may well leave a lasting mark, if not on the global economy then on research.
An Alternative Solution
The Zika epidemic set researchers around the world off on a race to develop a vaccine. Of course, vaccine research is an essential part of tackling a disease, but it has limitations. Vaccines are often developed with only a single disease in mind, and testing can take years to complete. As epidemics of mosquito-borne illness become more common, scientists are looking for alternative solutions. The prospect of genetically engineering mosquitoes to prevent disease transmission at the source is drawing increasing attention.
The use of modified mosquitoes is not a novel concept. But recent developments in gene-editing techniques such as CRISPR, a technique targeting and modifying or deleting DNA in order to alter the behavior of organisms, will likely make producing selectively modified insects far more efficient. Mosquitoes' genes can be altered to make them sterile or resistant to specific diseases, modifications that would decrease their effectiveness as vectors for viruses like Zika or Mayaro. Over the past year or so, several research teams have conducted successful trials to produce modified mosquitoes that could one day be used to combat various vector-borne illnesses.
In December 2015, the journal Nature Biotechnology published an article detailing the use of a genome editing tool called CRISPR-cas9 to create a gene drive system to reduce the reproductive capabilities of female mosquitoes, the main vector for malaria. The gene drive technique promotes a higher-than-normal inheritance rate for a specific gene and its encoded instructions, thereby increasing the percentage of a population that carries the trait with each successive generation. In this study, researchers introduced a mutation meant to suppress mosquito populations, making the transmission of malaria no longer feasible.
The idea got a boost in 2016 when the Bill and Melinda Gates Foundation announced that it would donate $35 million to Target Malaria, a project that focuses on gene drives to inhibit reproduction and promote disease resistance in mosquitoes. The modified mosquitoes are still not yet ready for release into the wild, but the rapidly advancing CRISPR technology may have shaved years off the development process. Once fully developed, Target Malaria's gene drive techniques could lower the costs associated with traditional methods for managing malaria — including mosquito nets and insecticides to mitigate the risk of infection and drugs to treat the disease.
Researchers have used similar techniques to tackle Zika and dengue. British biotechnology company Oxitec, for example, has modified mosquitoes of the species that transmits Zika with a self-limiting gene that prevents them from breeding in the wild. The company conducted successful trials with the modified mosquitoes in Brazil, the Cayman Islands, Panama and Malaysia. In August 2016, the U.S. Food and Drug Administration approved the insects for use in containing the Zika outbreak in Florida. Earlier this year, scientists conducting a different study altered mosquitoes to increase their resistance to dengue. The genetically modified mosquitoes in the study had normal lifespans but carried fewer copies of the dengue virus and produced fewer eggs than did insects in the control group. The goal may be to eventually use gene-drive systems to more rapidly pass on the resistance.
However promising these developments are, genetically modified mosquitoes will not rid the world of all its vector-borne diseases. And though they have come a long way, the gene-editing techniques involved still have several hurdles to clear. The legal battle for patent rights to the CRISPR system is in its final stages in U.S. courts. Environmentalists, meanwhile, still object to genetically modifying mosquitoes — a position that long predates CRISPR — for fear of the unforeseen repercussions of wiping out certain species. Changes in regulations, oversight and funding, especially under the new presidential administration in the United States, may also alter the timeline for implementing genetic modification as a tool to fight a wider array of vector-borne illnesses.