First population study of GM mosquitoes highlights difficulties facing malaria control technique

The first laboratory population study of genetically modified mosquitoes identifies issues that need to be faced in the task of turning mosquitoes from disease carriers into disease fighters.

Scientists from Imperial College London report in Science today that populations including genetically modified mosquitoes quickly lose their test marker gene when they are bred with unmodified mosquitoes.

The scientists say their results have several lessons for further work on developing GM mosquitoes, and they suggest a number of ways around the problems they have observed.

With no immediate prospects of a vaccine against the disease that affects more than 300 million people every year, novel strategies to tackle malaria are keenly sought. One strategy is to release a strain of mosquito into the wild that has been genetically engineered so it cannot transmit the malarial parasite.

Since the first GM mosquito was created three years ago at Imperial, scientists considering this approach have been examining the evidence from carefully-contained laboratory tests of how transgenic mosquitoes fare when mixed with populations of unmodified mosquitoes.

This study, which was funded by the Wellcome Trust, indicates that while the act of modifying mosquitoes does not have a major effect on their ability to survive, when the modified insects are placed in a natural population they have relatively low competitiveness.

Professor Andrea Crisanti of the Department of Biological Sciences, and senior author of the paper said: “These population studies are absolutely critical to the regulatory processes that will assess the safety and environmental consequences of this new technology.”

“They will help to assess the overall feasibility and costs of using GM mosquitoes to fight diseases such as malaria, yellow fever and dengue and play an important part in developing future strategies to banish these major scourges afflicting humanity.

“While more work is needed on the molecular genetics of this problem, an increasingly important challenge is to study the population biology of transformed mosquitoes and understand how a beneficial gene can be driven through a wild population,” he said.

The researchers used a stable and proven gene transfer technology to insert a green or red fluorescent marker into four different lines of the mosquito Anopheles stephensi, the major carrier of malaria in India.

In control population studies containing GM mosquitoes only, the fluorescent marker was maintained intact and passed on for over 30 generations. But when the GM insects were allowed to breed with unmodified mosquitoes the number of marker-carrying mosquitoes in the population decreased sharply, and in some experiments the marker disappeared entirely within 4-16 generations.

Professor Charles Godfray, Director of the Natural Environment Research Council (NERC) Centre for Population Biology at Imperial, and co-author of the study, carried out mathematical modelling of the mosquito population dynamics. This allowed the researchers to explore the different processes that might explain the performance of GM mosquitoes in a mixed population.

The authors suggested reasons for the poor performance of the mosquitoes carrying the inserted marker gene.

“By creating a strain of GM mosquitoes through breeding descendants of a single transformed individual, the introduced gene is likely to become associated with one or more deleterious mutations. Though these deleterious genes do not kill the GM mosquito, they cause it to lose out in competition with normal mosquitoes. The good news is that now we have identified these problems they can be mitigated by using crossing regimes that minimise the effects of inbreeding,” said the authors.