Genetically altered mosquitoes to close gaps in malaria fight
In 2020, nearly 6.9 million cases of malaria and about 742 deaths were confirmed in Kenya according to the Kenya Malaria Indicator Survey (KMIS) 2020.
Although the number of reported infections declined from 10.9 million in 2018, the disease is still one of the main health issues in the country despite being a largely preventable and treatable disease.
Kenya is not the only country suffering from the burden of this life-threatening disease. According to World Health Organisation (WHO) latest world malaria report, there were an estimated 241 million malaria cases and 627,000 malaria deaths worldwide in 2020. This represents about 14 million more cases in 2020 compared to 2019, and 69,000 more deaths.
The high number of malaria cases continues to be registered even though several efforts have been put in place towards malaria eradication. It is for this reason scientists and researchers are assessing the use of new tools to edit the genes of malaria-transmitting mosquitoes as they try to come up with a long-lasting solution towards control and elimination of this disease.
“The war against malaria has been ongoing for decades. It has led to the development of several interventions strategies, such as antimalarial drugs, insecticide-treated nets, and vaccines among others. However, despite all the interventions, the disease has not been eradicated because there are increased cases of insecticide resistance in mosquitoes, which pose a significant public health concern,” says Dr Willy Kiprotich Tonui, EBS, the Chairman and Executive Director at the Environmental Health Safety (EHS) Consultancy Limited who also doubles up as the Founder and Head of Secretariat to African Genetic Biocontrol Consortium.
The African Genetic Biocontrol Consortium is an interconnected network of organisations that strive to demonstrate the value of a regional forum centred on biocontrol dedicated to the development of genetic biocontrol strategies. Its main objective is to create awareness of how biocontrol developments impact our lives.
He says scientists are working day and night to see how genetic modification using gene drive technologies can be used to reduce malaria transmission in Africa by suppressing or modifying vector populations. This technology relies on the gene-editing tool CRISPR and some bits of RNA to alter or silence a specific gene or insert a new one. Once the new gene is inserted in one generation, in the next generation, the whole drive copies itself onto its partner chromosome so that the genome no longer has the natural version of the chosen gene, and instead has two copies of the gene drive. In this way, the change is passed on to up to 100 per cent of offspring. “Gene drive technology could be part of the answer that we have been waiting for malaria control and elimination. It is one of the newest approaches that is being tested as a potential strategy for eliminating malaria,” he said, adding, “The reason is that gene drive technologies will potentially reduce the incidence of mosquito-borne diseases, such as malaria in Africa and dengue fever in many parts of the world, resulting in healthier populations,” he said.
“However, for malaria eradication (that is the disappearance of every malaria parasite from the face of this country and planet) there is a need for an integrated approach that incorporates several control methods, such as insecticide-treated nets, indoor residual spraying, environmental management, vaccines, and genetic biocontrol methods such as gene drives,” he added.
Reduce malaria carrying mosquito
He reveals that the good thing about this technology when used for malaria control and elimination is that, its main aim is not to eliminate mosquitoes as many people have been saying since the modified population continues to exist and carries the drive gene at close to 100 per cent, but instead it reduces malaria carrying mosquito or unable to spread malaria.
However, in other areas, the tool is being used for suppression. For example, gene drive is a fundamentally new approach to invasive species control. The tool is currently being considered a humane, targeted way to wipe out alien pest species on Islands, such as mice, rats, and rabbits, by turning their own genes on themselves so they can no longer reproduce and their population collapses.
“With this tool, scientists are not looking into mosquito population suppression, which means knocking out the female fertility genes to prevent them from laying eggs or distort sex chromosome inheritance, because this will have some negative impacts on our ecosystem. Instead, they are looking into population alteration which entails a reduction of the vector’s ability to transmit disease by preventing the malaria parasite from binding to the receptors within the vector.”
He reveals that, apart from preventing diseases outbreaks, gene drive technologies in mosquitoes also envision several other possible uses, such as preventing transmission of malaria in Africa and other high incidence areas; preventing transmission of arboviruses, such as dengue or Zika in regions where they are prevalent, and controlling transmission of avian malaria that is threatening fragile native bird populations in island habitats.
“Although mosquito applications dominate the field of gene drives, scientists have also proposed ways to use the preferential inheritance that characterizes ‘gene drive’ to develop solutions for previously intractable threats to public health, food security, and biodiversity. For example, gene drive technologies have been proposed to address problems in public health, such as the transmission of arthropod-borne pathogens, problems in agriculture caused by insect pests, weeds, and plant pathogens, and problems in conservation caused by invasive species. Therefore, we may see experiments being tried for ticks, fleas, and others in the future.”
He says targeting malaria using gene drives is more cost-effective and feasible than traditional interventions, because gene drives only target specific species of mosquitoes that transmit malaria and not all species. Out of the 3,500 or so mosquito species that exist, only those within the Anopheles genus are capable of transmitting human malaria. Apart from that, if the insecticides resistance continues, there are risks that the malaria parasite will soon become resistant to drugs.
And will the release of GM mosquitoes to the wild stop the frequent malaria disease outbreaks? Dr Tonui says that gene drives will have the potential to limit the spread of malaria outbreaks to some extent, because the technology will ensure that in the long run there are reduced populations of mosquito species that can transmit human malaria.
Myths and misconceptions
However, studies are currently going on to establish whether genetically modified mosquitoes can achieve the ultimate goal of suppressing a wild population of potentially malaria-infected mosquitoes.
“What people need to know is that as of today, gene drive technologies are only being tested in the laboratory as part of ongoing research and development efforts, not outside, that is why most questions remain unanswered,” he explains.
To demystify some myths and misconceptions that have been there about the genetically modified organism, he says that people should stop fearing that gene introduced into mosquitoes would find its way into the human genome because this scenario has virtually no chance of happening in the foreseeable future.
Dr Tonui says most gene drive systems are constructed so that the gene drive is active in only certain cells of the reproductive system and at a certain time that is either during the formation of sperm or eggs.
These temporal and spatial constraints are important and are achieved through the use of DNA sequences that exhibit these properties only in the species from which they were obtained. These molecular components of the gene drive are highly unlikely to function within a human cell as they do in mosquito cells. “The fact that each of these events individually has extremely low improbable means that taken together with the probability of a functional gene drive being transferred from the cells of mosquitoes to the cells of humans, other animals is exceedingly low,” he offers.
However, determination of the ecological risks posed by GM mosquitoes, transboundary movement, and consequences to the entire ecosystem are issues of concern that are currently being studied.
On the issue of whether it would have been better to spend all the time and money developing a vaccine against malaria instead of such as solution, he says that though vaccines are important tools against several infectious diseases, unfortunately, despite decades of effort, it has not been possible to come up with a vaccine for malaria and dengue.
The reason is, that the two are very challenging diseases to control and there is little doubt that successful control and/or elimination will require multiple different tools, with vector control remaining important with or without available vaccines. That is why there is need for an integrated approach.
And are there countries that have released genetically modified mosquitoes to the wild since research has been ongoing for quite some time? Though gene-drive research is moving fast, Dr Tonui notes that only one country, the United States, has been able to approve release of GM mosquitoes into the wild. This is after the Environmental Protection Agency recently gave a green light to Oxitec, a US-owned company, to release over 2 million genetically modified mosquitoes in Florida and California as part of an expanded effort to combat the transmission of diseases such as Zika and Dengue fever.