A Great Day for Mankind: Malaria could be soon a thing of the past.
Scientists have hailed the genetic modification of mosquitoes that could crash the insect’s populations as a “quantum leap” that will make a substantial and important contribution to eradicating malaria.
Previous efforts to tackle the disease, which kills more than a million people each year – most of whom are African children – have included bed nets to protect people and insecticides to kill the mosquito species most responsible for the transmission of malaria ( Anopheles gambiae).
The technique by a team at Imperial College London involves injecting mosquitoes with a gene that causes the vast majority of their offspring to be male, leading to a dramatic decline in population within six generations as females disappear.
“You have a short-term benefit because males don’t bite humans [or transmit malaria],” said Professor Andrea Crisanti, one of the authors of the new research, which was published in the journal Nature Communications on Tuesday.
“But in the long term you will eventually eradicate or substantially reduce mosquitoes. This could make a substantial contribution to eradicating malaria, combined with other tools such as insecticides.”
The scientists injected mosquitoes with a gene from slime mould – a homing endonuclease or enzyme called I-PpoI – which attached itself to their X chromosome during the male’s sperm-making process and effectively shredded part of the chromosome’s DNA. The result was that more than 95 per cent of the mosquitoes’ offspring were males. The researchers found that the modified mosquitoes mated with wild mosquitoes, creating fertile mosquitoes which then overwhelmingly produced male offspring, passing on the gene.
“Under field conditions the accumulation of X chromosome damage would significantly contribute to the demise of target populations,” the scientists say in their paper.
“The engineering is a quantum leap in terms of what has been done before,” said Crisanti, who worked on previous research in 2008, which took a similar approach but unintentionally resulted in sterile mosquitoes, meaning the gene’s ability to spread was limited.
Imperial College London also published work in 2011 on a distinctly different approach to impair the fertility of mosquitoes generally, rather than distorting the make-up of their sex.
Dr Luke Alphey, group leader of the vector-borne viral diseases programme at the Pirbright Institute, who was not involved in the latest research, called it a “big step forward” and said field trials could be conducted after further testing. “The overall goal of this research programme is even more 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,” he said.
Dr Michael Bonsall, reader in zoology at the University of Oxford, described the research as “super cool work”and said: “This has important implications for limiting the spread of malaria.”
Dr Thomas Walker, lecturer at the London School of Hygiene and Tropical Medicine, said that the work was “very good science” and “very promising”, but said any uncertainty was in how the GM mosquitoes would fare out of the laboratory and in the field.
Dr Helen Williams, director of GeneWatch UK, a not-for-profit group that has been critical of previous GM mosquito research, warned of the unintended consequences of crashing mosquitoes’ populations. “We would want to ensure that the risks are properly considered before GM mosquitoes are released into the environment. For example, reducing the population of one mosquito species can increase the population of other mosquitoes, so you can potentially make it worse. If you change an ecosystem and remove a species, another species often moves into that niche.”
And here is the abstract of Professor Crisanti study:
Regulation of Anopheles gambiae male accessory gland genes influences postmating response in female
Tania Dottorini*,‡, Tania Persampieri*, Pietro Palladino*, Dean A. Baker§, Roberta Spaccapelo*, Nicola Senin† and Andrea Crisanti*,‡,1
+ Author Affiliations
*Department of Experimental Medicine and
†Department of Industrial Engineering, University of Perugia, Perugia, Italy;
‡Department of Biological Sciences, Imperial College London, South Kensington Campus, London, UK; and
§Department of Genetics, University of Cambridge, Cambridge, UK
↵1Correspondence: Department of Biological Sciences, Imperial College London, South Kensington Campus, SAF, London, SW7 2AZ, UK. E-mail: [email protected]
In Drosophila, the accessory gland proteins (Acps) secreted from the male accessory glands (MAGs) and transferred along with sperm into the female reproductive tract have been implicated in triggering postmating behavioral changes, including refractoriness to subsequent mating and propensity to egg laying. Recently, Acps have been found also in Anopheles, suggesting similar functions. Understanding the mechanisms underlying transcriptional regulation of Acps and their functional role in modulating Anopheles postmating behavior may lead to the identification of novel vector control strategies to reduce mosquito populations. We identified heat-shock factor (HSF) binding sites within the Acp promoters of male Anopheles gambiae and discovered three distinct Hsf isoforms; one being significantly up-regulated in the MAGs after mating. Through genome-wide transcription analysis of Hsf-silenced males, we observed significant down-regulation in 50% of the Acp genes if compared to control males treated with a construct directed against an unrelated bacterial sequence. Treated males retained normal life span and reproductive behavior compared to control males. However, mated wild-type females showed a ∼46% reduction of egg deposition rate and a ∼23% reduction of hatching rate (∼58% combined reduction of progeny). Our results highlight an unsuspected role of HSF in regulating Acp transcription in A. gambiae and provide evidence that Acp down-regulation in males leads a significant reduction of progeny, thus opening new avenues toward the development of novel vector control strategies.—Dottorini, T., Persampieri, T., Palladino, P., Baker, D. A., Spaccapelo, R., Senin, N., Crisanti, A. Regulation of Anopheles gambiae male accessory gland genes influences postmating response in female.