It is nearly five o’clock in the evening when the bright lights in the ceiling are dimming, while an orangish light is appearing from the back end of the room, mimicking the sunset, creating a clear contrast with a dark panel on the floor to simulate the horizon. This is the signal that hundreds of male mosquitoes were waiting for their most important daily activity: they start to fly in a circle mid-air like a dance over a black square marker on the floor, looking for females to mate with. Anopheles mosquitoes, the vector of human malaria, usually mate in swarms at dusk, and soon after, mated females begin their search of a prey (usually large mammals) to suck up the blood they need to produce eggs. Here, at the Genetics and Ecology Research Centre of Polo of Genomics, Genetics and Biology (Polo GGB) in Terni (an hour drive north of Rome, Italy) we feed our mosquitoes with a synthetic membrane loaded off cow blood.
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On the 20thand 21stof June 2019, CRISPRcon organised a conference on conversations on science, society and the future of gene editing at Wageningen University in The Netherlands. This event was a great platform to network, share and learn experiences on how gene editing and other technologies can solve major agricultural and health problems.
The release of genetically modified sterile male mosquitoes in Burkina Faso is a very important milestone for our project. It is the first of its kind on the African continent and our team has been working since 2012 to reach this point.
It is this time of year again, when on the 25thof April researchers, NGOs, civil society groups, corporate sector, governments reinstate their will and efforts to contribute to malaria eradication on the occasion of World Malaria Day.
For some this day might seem redundant. However, it has never been as important for people working towards malaria eradication and people affected by this deadly disease to join their voices and reaffirm the need to continue our efforts. Since 2016 the World Malaria Report has showed that progress against malaria has plateaued and that in some countries and regions malaria cases are increasing.
This plateau is a clear call for the development of new innovations and continuous efforts and investments in Research and Development if we are to find and curve new solutions to save millions of people’s lives from malaria worldwide.
If you think about the kind of science needed to develop a genetic technology to control malaria mosquitoes, I wonder if modelling springs to your mind? If not, you may well wonder – what is it, and why do we do it?
A good definition for ‘model’ is a simplified representation or description of a complex entity. This applies to human models (they are supposed to be ‘idealised humans’, at least in appearance!), to wooden models of mosquitoes, and to mathematical models of mosquito populations.
As we start a new year, I would like to take the opportunity of looking back at our accomplishments in 2018. Our work spans the full range of activities needed to develop novel genetic control tools for malaria control and bring them to the field, and good progress was made on all fronts.
First, Andrea Crisanti’s lab published a paper demonstrating for the first time that a genetic construct, introduced at low frequency into a lab population, can spread through the population over successive generations and cause it to crash. This success was the result of careful attention to the problem of resistance, and devising ways to avoid it, and demonstrated the power of gene drive to control mosquito populations.
Second, our success will depend on us getting regulatory authorization to test our constructs in the field. We believe that the first modified mosquitoes to be released in Africa should not contain a driving construct, and that an appropriately cautious approach calls for initial studies using non-driving strains. To that end, we have developed a male-sterile construct which has been imported by Abdoulaye Diabate’s lab into Burkina Faso and crossed into a locally-derived genetic background. This past year we obtained regulatory authorization from the National Biosafety Agency in Burkina Faso to conduct a small-scale release of this strain, the first of its kind in Africa, and we hope to make the releases in 2019. At a broader level, it is vitally important that the various regulatory authorities remain open to considering future applications to release gene drive constructs. At the Convention on Biological Diversity (CBD) meeting in November in Egypt there was an effort by some campaign organisations to have a blanket moratorium on such releases, and it was gratifying to see the overwhelming majority of countries reject that idea, and the positive result of the negotiation being a text emphasising the need for case-by-case assessment of any particular proposal on its own merits and risks.
Third, ecological studies are also critical to our success, as the most common question we get from our various stakeholders is about the ecological consequences of reducing populations of our target species, Anopheles gambiae and relatives of the species complex. The consensus expert opinion of ecologists who know these species is that they are not “keystone” species and reducing their population is unlikely to have ramifying effects on the wider ecosystem. Indeed, in some parts of East Africa bednets have been successful in dramatically reducing their numbers, and there have not been reports of obvious ecological consequences. Reinforcing this idea, John Mumford’s group published an important review of the ecology of An. gambiae mosquitoes, which concluded that there is unlikely to be a predator that specifically relies on them for food. To further explore this issue, we have this past year started field studies in Ghana to understand who eats whom in the relevant ecological communities.
Fourth, project success will depend on there being sufficient capacity on the African continent to implement properly. To that end, we have been building a new insectary facility at the Uganda Virus Research Institute, installed new offices at the Institut de Recherche en Sciences de la Santé (IRSS) campus in Burkina Faso, and published a clutch of papers on “facility readiness” [1, 2, 3 & 4]. And, for the second time, we have run a 3-day short course on gene drive for malaria control in collaboration with the Pan African Mosquito Control Association (PAMCA), as a side activity to their annual meeting. This is a key component of engaging and training the next generation of researchers, which itself will be essential to the success of our project.
There is a buzz within the Malaria Research and Training Center, which is set within the lush green grounds of the University of Sciences, Techniques and Technologies of Bamako, Mali.
Along one of the university’s many tree-lined paths is the recently renovated insectary, which today houses two mosquito colonies used by the team. One is a local wild Anopheles coluzzii strain established from mosquitoes captured in local villages, which was brought into the lab for individual oviposition (egg laying) and molecular identification, and is maintained in the insectary for future studies. The other is a strain of Anopheles gambiae sl mosquito that has a naturally occurring (i.e. non-genetically modified) heritable trait that causes a white pigment “collar” on the back of the mosquito larvae, which can be visualised under a microscope by a trained eye. The colour variant strain can be maintained by selecting specific colour variant female mosquitoes (that have the white “collar” pigmentation), and crossing them to male mosquitoes that do not.
From 16th to 29th November, the world converged to Sharm El Sheikh, Egypt, for the Conference of the Parties of the Convention on Biological Diversity. This event gathered the parties signatory to the convention, non-parties, as well as observers from the civil society, indigenous people and local communities, as well as researchers.
At Target Malaria in Burkina Faso, we are currently working on the first phase of our research – a genetically modified sterile male mosquito. The team in Burkina Faso has been working on the genetically modified sterile male mosquito in our contained insectary at the Institut de Recherche en Sciences de la Santé (IRSS) since its importation in November 2016 in Bobo-Dioulasso from Italy.
Delegations from all over the world are converging to Egypt for the opening this week of the Conference of the Parties of the Convention on Biological Diversity and related protocols.
This is a crucial time for research on innovative vector control against malaria using gene drive approaches. Decision-makers have the opportunity to reaffirm the importance of enabling research to support responsible innovation and evidence-based decision-making.