How genetic modification in mosquitoes could accelerate malaria elimination efforts

ABIDJAN — A genetic alteration technique known as “gene drive” could help to suppress — and potentially eliminate — malaria-infected mosquito populations, a new report has shown.

The technique is designed to sterilize females over time, reduce offspring, and eventually lead to a male population that collapses.

Last week, Target Malaria scientists at Imperial College London reported that, for the first time, they had successfully wiped out an entire population of mosquitoes in a laboratory using gene drive.

The measure allows a genetic modification to progressively increase within a particular population by ensuring that it is passed down to a higher number of offspring than usual. In this case, scientists modified a gene called “doublesex,” which was formed millions of years ago and plays a role in sex differentiation.

“We have destroyed a particular portion of this gene which is responsible for female development [so] that the male develops effectively normal … The female, when inheriting two copies of the damaged gene [from her mother and father], develops [as] intersex, having some male and female features,” lead biologist Andrea Cristiani explained.

Experiments with the Anopheles gambiae species led to females being unable to bite or reproduce, resulting in fewer offspring over generations, and eventually leading to an all-male population by the eighth generation.

“This is a process that many are hoping will lead to the possibility of suppressing or even eliminating malaria and potentially other vector-borne infectious diseases,” James Collins, ecology professor and researcher at the National Academies of Sciences, Engineering and Medicine, told Devex.

The test seems to have overcome one of the known limitations of gene drive technology: Resistance. Typically, with a disruption to genetic makeup, organisms would end up with selection against the gene drive being successful, Collins said. But while it is encouraging that scientists have surpassed one obstacle, he remains cautious about claiming it as a victory against malaria.  

“From my point of view, they need to demonstrate that this will work in larger populations since larger populations will have more genetic variations and the likelihood of selection against the gene drive increases,” Collins noted.

Target Malaria, an international research consortium funded by the Bill & Melinda Gates Foundation, will continue experimenting with gene drive technology using a phased testing approach, expanding to larger laboratory enclosures, then a confined field, followed by staged environmental release with surveillance in the wild. With more advanced testing, scientists will attempt to reproduce complex, tropical environmental conditions similar to malaria-endemic environments.

“We will use this time to collect a number of data: The fitness of the mosquitoes, stability of the [gene] drive, the ability of the drive to move across a species, and food web analysis to determine where mosquitoes sit in the ecosystem,” Cristiani explained.

The idea of eliminating an entire species from an ecosystem could pose ecological and social concerns such as the destruction of food webs and disruption to agriculture, experts warn.

“Suppressing the mosquito population will minimize the disease burden as far as human populations are concerned but we have an imperfect understanding of what the removal of those mosquito populations will do relative to the entire ecosystem,” Collins added.

Cristiani argues, however, that with more than 800 mosquito species in Africa, it is “reasonable to assume that another species would fill the ecological niche left by the elimination of the modified insects.”

Target Malaria asserts that eliminating an entire species of malaria-carrying mosquitoes is not the objective, but rather eliminating malaria itself — and the recent findings that suggest it is possible to suppress a particular mosquito species could be enough to break the cycle of transmission.

Malaria cases failed to fall in 2016 despite well-funded campaigns and increased access to malaria control interventions worldwide. According to the World Health Organization, Africa continues to account for 90 percent of malaria cases and 91 percent of malaria deaths.

Collins called the outcome of this experiment a “promising step along the way” in the effort to eliminate malaria by 2030.