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Making male mosquitoes

20 Oct, 2014

A bit of genetic trickery may hold the key to controlling the spread of mosquito-borne diseases such as malaria.

Scientists genetically modified mosquitoes in the lab to produce sperm lacking an X chromosome, ensuring that predominantly male offspring were created. This approach to reduce the female mosquito population heralds a new way of eradicating or controlling malaria and other mosquito-borne diseases.

Led by Professor Andrea Crisanti and Dr Nikolai Windbichler from the Department of Life Sciences at Imperial College London, a team of UK, US and Italian scientists genetically modified Anopheles gambiae mosquitoes in the lab to produce sperm lacking an X chromosome, ensuring that predominantly male offspring were created. As most pest population sizes are determined by the number and productivity of females, the approach heralds a new way of eradicating or controlling malaria and other mosquito-borne diseases.

It took some 6 years of research for the researchers to develop a modified enzyme, called I-PpoI, to target and destroy a specific region of the mosquito’s X chromosome during production of sperm, resulting in unaffected fertility (the mosquito can still breed) but almost no functioning sperm carrying the female X chromosome.

When the modified mosquitoes were introduced to five different caged wild-type mosquito populations, the modified subjects produced more than 95% male offspring, effectively suppressing their population size by the second generation as there were fewer females to breed with. What’s more, the researchers observed that the modified genes were passed on to the next generation of males, making the process self-sustaining. In four of the five caged population, the entire population was eliminated within six generations, with fewer and fewer females in each generation.

The Anopheles gambiae mosquito is the main transmitter of the malaria parasite (genus Plasmodium), with the female of the species the one doing the biting. The parasite is transmitted to the human bloodstream by the bite, where it travels to the liver to mature and reproduce. The parasite typically causes fever, chills, vomiting and headaches in its human host, as well as a raft of side-effects such as trouble breathing, kidney failure, enlarged liver, miscarriage, stillbirths and preterm births. In severe cases, the disease progresses to coma or death.

In an interview with the Science Media Centre in the UK, Dr Michael Bonsall, a Reader in Zoology at the University of Oxford, said it will be exciting to see how this latest research is taken forward.

“It’s important to note this piece of work is at a very early stage and is a long way from being deployed. Before a modified mosquito could be released into the environment, it would have to pass through a very rigorous regulatory framework.

“In an intervention like this, we have to weigh up the environmental effects against the human health effects. On the one hand, this species of mosquito is a stagnant water breeder, eaten by fish, but not relied on as a food source – fish have a very varied diet. Similarly, it doesn’t eat anything that has to be kept in check. On the other hand, a million children die every year from malaria. We can’t afford not to take this approach seriously.”

Recent medical advances, prevention and control measures have reduced malaria mortality rates substantially, but in many African regions, the disease remains prevalent. Malaria parasites are developing resistance to available drugs, and mosquitoes are developing resistance to insecticides. The World Health Organisation estimates that some 3.4 billion people – half the world’s population – are at risk from contracting malaria. In 2012, approximately 207 million people contacted the disease of which some 627 000 people died – 90% of these deaths occurred in Africa, mostly among children under 5 years. Others are often debilitated for life.

In another interview with the UK SMC, Dr Luke Alphey, a Group Leader in the Vector-borne Viral Diseases Programme at The Pirbright Institute, says the overall goal of this research programme is ambitious: “to develop a version of this genetic system that will spread itself through the target species, removing females and causing population crash or extinction as it goes”.

“If this species were to suffer a population crash, it’s hard to see how significant negative side-effects might arise. The mosquitoes are not keystone species in their ecosystems. No other animal is dependent on them for food, and we don’t rely on mosquitoes to eat anything. They don’t seem to keep out anything more dangerous, not least because they are the most dangerous thing around, and this technique only affects one species, Anopheles gambiae, among over 3000 known species of mosquitoes.

“If we rely instead on pesticide control, we would likely kill non-malarial mosquitoes and many other insects besides. The genetic approach is much more precise.

“As well as considering potential dangers of controlling this species of mosquito, I would equally consider the dangers of not intervening. Malaria is a major killer, and if we’re serious about saving lives, it’s going to take scientific innovation like this.”

References

Galizi, R., Doyle, L.A., Menichelli, M., Bernardini, F., Deredec, A., Burt, A., Stoddard, B.L., Windbichler, N. and Crisanti, A. (2014). A synthetic sex ratio distortion system for the control of the human malaria mosquito. Nature Communications. 5:3977. doi: 10.1038/ncomms4977. Published online ahead of print 10 June 2014.

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