Making mosquitoes male may manage malaria
"Mosquitoes modified to only give birth to males in bid to wipe out malaria," The Daily Telegraph reports after new research has found an innovative way of tackling the global problem of malaria.
The technique used in this latest research is both brutal and elegant. Female mosquitoes, which spread malaria to humans through their bite, were genetically modified so that their offspring were overwhelmingly (95%) male. This male-only trait was inherited and repeated with future generations, and has the potential to wipe the species out.
It is not yet known if the genetically modified mosquitoes are able to compete with wild mosquitoes in their natural environment, as the studies have so far only been conducted in cages in a laboratory.
If the mosquitoes can have an effect in the wild, in the short-term this could reduce the spread of malaria by cutting the number of female mosquitoes. In the long-term, the species could potentially be completely eliminated.
Future studies would have to ensure that wiping out the type of mosquito that carries malaria does not upset the ecosystem and cause more problems.
A famous example of this type of ecological upset is the introduction of cane toads in Australia to manage the beetle population. The toads proved highly adaptive to the environment and are now a major pest.
Where did the story come from?
The study was carried out by researchers from Imperial College London, the University of Perugia in Italy, and the Fred Hutchinson Cancer Research Center in the US.
It was funded by the US National Institutes for Health and the European Research Council.
The study was published in the peer-reviewed medical journal, Nature Communications. It is open access, so it is free to read online.
The UK media's coverage was good, with The Guardian providing expert comments on the study balanced by a quote from Dr Helen Williams, director of GeneWatch UK, regarding the potential risks of interrupting the ecosystem.
What kind of research was this?
This was a laboratory study of mosquitoes that aimed to find a way of reducing their numbers, as female mosquitoes – which bite humans – spread malaria.
The number of female mosquitoes in the mosquito population and their speed of reproduction are both believed to be ways of controlling their population size. If there was a way to increase the proportion of male offspring, this could therefore reduce the population size.
Previous attempts in caged experiments using naturally occurring mutations – which gave a higher number of male offspring in two types of mosquito called Aedes and Culex – were unsuccessful because the females had a natural resistance to them.
The researchers aimed to genetically modify mosquitoes using a synthetic enzyme, based on the naturally occurring mutations, to damage the X chromosome in males. This would mean that they are potentially only able to pass on the Y chromosome during reproduction, thereby only producing male offspring.
What did the research involve?
The researchers investigated the effect of different enzymes on damaging the X chromosome of male mosquitoes in the laboratory and then performed various experiments using live mosquitoes.
They created an enzyme that targets and damages the X chromosome in the male mosquito species Anopheles gambiae, which carries malaria.
The researchers ensured that the process only damaged the X chromosome in the male mosquito and did not affect the Y chromosome so that the offspring were not sterile.
If they were sterile, they would not be able to reproduce and the effects of the genetically modified mosquitoes would be limited to one generation.
This would then require an unimaginable number of mosquitoes to be injected for there to be any impact on numbers.
The researchers performed various experiments to see if the genetic mutation would be passed on to future generations.
They tested the level of damage to the X chromosome caused by various enzymes and at different temperatures until they found the optimal genetic modification that was able to produce mostly males without affecting the fertility rate.
What were the basic results?
The offspring of genetically modified male mosquitoes were more than 95% male. The enzyme that damages the X chromosome was inherited by these males, causing them to have male offspring.
In five independent cage experiments, putting in three times the number of genetically modified males to normal males caused the suppression of the wild-type mosquito. All mosquitoes were eventually eliminated in four of the cages within six generations.
In the small fraction of female offspring produced by the genetically modified males, their offspring were mostly female when they were fertilised by wild male mosquitoes.
The male offspring had a 50% chance of having the genetic modification. When they were crossed with wild female mosquitoes, however, they were still more likely to have males.
How did the researchers interpret the results?
The researchers concluded that, "Distorter male mosquitoes can efficiently suppress caged wild-type mosquito populations, providing the foundation for a new class of genetic vector control strategies."
However, they acknowledge that, "The robustness of these traits under variable natural conditions remains to be studied."
Conclusion
This study found that genetically modifying the X chromosome in male mosquitoes can cause more than 95% of their offspring to be male in caged experiments. This genetic modification is inherited by these offspring, who then have similar high numbers of male offspring.
While these results are promising, it is not clear whether the small fraction of female offspring would be enough to eventually reverse the process and create mosquitoes resistant to the effects of the enzyme.
These studies were just performed on the species Anopheles gambiae, which carries malaria. It is not yet known what effect reducing or eliminating the species would have on the population size of other mosquitoes or the ecological system.
This would need to be considered carefully before any genetically modified species was released into the environment. Our ecosystem is incredibly complex, so tinkering with it could lead to a range of unexpected and unwanted consequences.
