Amazing breakthrough: genetic engineering gives mosquito control a boost

Throughout the history of mankind, mosquitoes have always interfered in human life, annoying us by constantly biting us and sometimes causing damage by spreading deadly diseases. The earliest known mosquitoes in the fossil record date back at least 70 million years, and evidence of mosquito-borne diseases such as malaria dates back to Egyptian corpses as far back as 2000 BC.

Besides malaria, which kills more than half a million people every year and affects about 250 million people, mosquitoes carry a variety of other diseases. These include dengue, Zika, lymphatic filariasis, and yellow fever. Understandably, the relationship we have with these blood-sucking insects is not at all.

Help from sequencing technology

The rapid urbanization of the world’s population, especially in many developing and economically developing countries such as India, has led to an increase in mosquito-borne diseases such as dengue every year. Along with climate change and its alarming effects, mosquito-borne diseases have expanded into new territories. A notable example is the endemic cases of dengue in France in recent years.

It is not surprising that the control of mosquitoes has taken a big place today and the battle continues without end with a range of tools – from mosquito nets to insecticides and the use of symbionts like. Wolbachia. But with anti-malarial drug resistance rising at an alarming rate, new methods of mosquito control have been forced to gain prominence, despite the availability of a first-generation anti-malarial vaccine that officials in various countries are currently testing in endemic areas.

In the last twenty years, our ability to read or sequence the genomes of organisms, and to edit and manipulate these genomes, has given us new tools in this fight. Thanks to advances in next-generation sequencing techniques, we now have access to the entire genome sequence of many mosquito species. Notably, researchers from the University of California, the Tata Center for Genetics and Society, and the Center for Bioinformatics and Applied Biotechnology have helped prepare the high-quality genome. Anopheles stephensi, the main mosquito that carries malaria. (The latter two institutions are based in Bengaluru.)

The availability of this high-quality sequence, combined with our ability to genetically engineer it, offers unprecedented opportunities.

The gene drive

The basic idea behind the genetic modification of mosquitoes is to systematically control their population by interfering with their reproduction. Scientists around the world have developed different ways to modify genes. Central to this effort is gene-drive technology, the result of which is that mosquitoes select a specific inheritance, rather than inheritance following Mendelian genetic laws.

This technology was developed by Austin Burt, a professor at Imperial College London, in a 2003 paper published in Proceedings of the Royal Society. Here, the protein cuts the mosquito’s DNA in a region that does not code for a specific sequence in the genome. This triggers a natural mechanism in the cell that contains the DNA to repair it and forces the cell to insert the sequence, called run the sequencein the damaged part.

Several gene-drive versions have been documented in the literature, but all aim to reduce the reproductive capacity of mosquitoes or give them offspring. As a result, the malaria parasite will not be able to replicate inside the mosquito’s gut. In a recent paper on Advances in Science, researchers at Imperial College London have modified a gene expressed in mosquitoes to produce two anti-viral substances called maginin 2 and melittin. They are harmful to Plasmodium parasite growth in the midgut and shortens the life of female mosquitoes. Computational modeling studies have suggested that this approach could significantly disrupt malaria transmission.

Benefits and risks

In 2020, the US Environmental Protection Agency authorized the release of a genetically modified mosquito called OX5034 in Florida and Texas. Oxitec developed this mosquito with a gene that is sensitive to the antibiotic, tetracycline. The authorization followed extensive field trials conducted by the Brazilian company. The genetically modified OX5034 mosquitoes mated with female mosquitoes but the self-limiting gene prevented the female offspring from surviving. As a result, male mosquitoes will disappear from the environment after twelve generations.

Genetically modified mosquitoes have been used abroad but are under control in India, Brazil, and Panama. Early results from the trial showed a promising drop in mosquito numbers, about 90% during the trial. Further trials have shown that such technology can significantly reduce the incidence of dengue.

These technologies can bring benefits and risks, in different ways. The immediate implication is that drastic reductions in mosquitoes can alter food chains and ecosystems that include mosquitoes. So it is possible that a gap in the food chain may be ‘invaded’ by other mosquitoes or indeed by other insects. Therefore, we do not fully understand the short and long term impacts. And since the results will be shared by people, communities, and citizens, respectively, it means that the right decision and which procedures to follow are often a problem for policy makers.

An endless struggle

It is not surprising then that mosquito genetic engineering and experiments involving genetically modified mosquitoes have faced many challenges in different parts of the world. Critics have expressed concern about side effects, such as unintended environmental disruption or the potential for engineered genes to spread beyond the target mosquito population.

Some of these concerns are legitimate and require extensive data collection, close monitoring, and multi-stakeholder discussions regarding the adoption of these technologies. Closer to home, on the regulatory side, the Department of Biotechnology issued comprehensive guidelines for genetically engineered insects earlier this year. They provide a road map for researchers, explaining the procedures and regulations for working with such insects in the country.

The battle between mosquitoes and humans seems to be a timeless struggle, a testament to human ingenuity against evolutionary troublemakers.

The authors are senior consultants at Vishwanath Cancer Care Foundation.