The Gorgas Institute of Public Health in Panama is preparing to conduct the first releases of Oxitec mosquitoes in a residential suburb of the Arraijan District, west of Panama City. The trial targets the dengue virus-transmitting mosquito Aedes aegypti, and will start against a backdrop of a 2013 dengue epidemic that saw over 3,000 cases in Panama, more than treble the number in 2012.
The Gorgas Institute is named after William Crawford Gorgas, famed for his mosquito control work during the construction of the Panama Canal. Mosquito-transmitted malaria and yellow fever caused the death of 22,000 people between 1881 and 1889, resulting in the failure of a French effort to build the canal. In 1904, construction started again, and William Gorgas was drafted in to protect workers and locals from these diseases. By implementing mosquito control methods, tackling mosquito breeding sites and quarantining infected workers, malaria was largely controlled and yellow fever eliminated from the area by 1906. The Gorgas Institute continues in this vein and is a world leader in developing new approaches for controlling disease-carrying mosquitoes.
Following a recommendation from Panama’s National Biosafety Committee, and formal approval from the Ministries of Agricultural Development and Commerce and Industry, an open-field evaluation of Oxitec’s mosquitoes will be conducted by the Gorgas Institute, with technical support from Oxitec. Extensive community education and engagement will be an integral part of the evaluation.
The field evaluation will run for several months during which Gorgas researchers will aim to reduce numbers of Aedes aegypti. In previous evaluations of Oxitec’s mosquitoes, Aedes aegypti populations in the Cayman Islands and in Brazil have been supressed by 80-96%.
Dr Nestor Sosa, Director of the institute, said:
“Dengue fever is a growing concern in Panama, and the tools we have for controlling the dengue mosquito are limited and increasingly ineffective. There is a real need to explore additional, more effective technologies for combatting this pest and tackling the dengue problem.”
“Oxitec’s approach has already shown great promise. It’s a technology that is completely specific to the dengue mosquito we’re targeting, and by helping to reduce our reliance on chemical pesticides, it could also be beneficial for the environment.”
“We’ve worked closely with Oxitec and with local communities here in Panama to bring this project to the evaluation stage, and I’m delighted that we’re now able to take this next step. People in Panama know as well as anyone the toll that dengue fever can exact on a community: this exciting new technology may offer real hope for a future free from dengue.”
The mosquito production facility within Oxitec do Brasil’s Campinas headquarters, near São Paulo, was approved in the CTNBio meeting held on March 5-6th 2014. The approval includes all Oxitec’s genetically engineered insects, including Oxitec’s strain of the dengue mosquito Aedes aegypti.
Prior to the approval being given, inspectors from CTNBio visited the facility and were shown the procedures and equipment for the rearing of the dengue mosquito and for waste disposal and reviewed Oxitec’s biosecurity manual.
At the same meeting, CTNBio also approved the import of eggs from our UK facility in order to start a colony at the Campinas site. Over the coming weeks, the local team will begin production, initially on a test basis, to confirm the quality of the strain. Once the unit is running at full capacity it will be able to produce around 2 million male adult mosquitoes per week.
This production capacity is intended to enable a rapid start to mosquito control projects that Oxitec do Brazil undertakes after approval for open release is received. Additional capacity will be created as and when the need arises, to supply the mosquito control projects.
Through our involvement in projects to study and suppress local populations of the dengue fever mosquito Aedes aegypti in Brazil, the Caribbean, Malaysia and Panama, we have learned an enormous amount about how we will operate future large-scale mosquito management programmes. Understanding how far the mosquitoes fly, for example, informs us how many release points we need in a given area to achieve complete coverage of a target mosquito population. The average lifespan of our male mosquitoes in the field tells us how frequently we should release more to maintain a stable number in a town. We have collected large amounts of data on how our mosquitoes perform in the field, and how this affects the local target pest population.
With this knowledge, we have been able to map out our strategy for larger-scale dengue vector control operations, such as that being conducted by Moscamed with Oxitec male mosquitoes in Jacobina, a town of 50,000 inhabitants. Oxitec’s vector control programmes comprise three phases, which we call ‘Intervention’, ‘Clean-up’ and ‘Maintenance’. During all of these phases, we collect data on how many Oxitec males we release, where they are released and when. We also monitor the local mosquito population across the control programme area, using traps that capture adult mosquitoes and also ‘ovitraps’ in which female mosquitoes lay their eggs. With these data linked to a modern GIS mapping system, we are able to closely monitor how well the programme is working, and indicate areas where we should apply more or fewer males. The monitoring process is enabled through a coloured marker which is present in all our mosquitoes and their offspring, and is clearly visible under specialised filters. This means we can track our mosquitoes in terms of where they go, how long they live and how they perform.
The ‘Intervention’ phase is intended to bring a typical large standing population of the dengue mosquito down to a very low level. This phase therefore requires releases of Oxitec male mosquitoes in numbers sufficient to out-compete the local males for female mates. When most local female mosquitoes are being mated by Oxitec males, the local population will start to crash. In programmes to date the reduction of the target mosquito population to very low levels has taken about 6 months.
When dry, Aedes aegypti eggs can remain dormant for up to 6 months and will hatch when coming into contact with water. So in the second phase of the programme – the ‘Clean-up phase’ – sustained releases of Oxitec males will continue, but now in much smaller numbers. This phase is designed to clear up these pockets of residual mosquito populations, which typically include these egg banks that can serve as sources of re-infestation.
Once the wild population has been largely eliminated we enter the on-going ‘Maintenance phase’, which is designed to stop resurgence of the local mosquito population, which might happen by immigration from outside the programme area. One of the benefits of the Oxitec approach over most other control methods is that, as the wild pest population decreases, the effectiveness of releases increase as it becomes easier to outnumber the remaining wild males with released Oxitec males. In contrast, most conventional pest control methods struggle to target the remnant local population. During this Maintenance phase the solution can be adapted to local circumstances, such as seasonality of rainfall, and adequacy of local monitoring.
A similar strategy will be followed for our other products in development, including those for agriculture. For seasonal pests, our most effective strategy will generally be to use our products as a preventive measure, targeting the seasonal pest population before it is able to expand.
Humans are responsible for the spread of Aedes mosquitoes around the globe, and mosquito-borne diseases follow. First identified in the 1950s, chikungunya is caused by the chikungunya virus (CHIKV) and shares many symptoms with dengue fever, but is actually a distinct disease. Like dengue, it causes fever, muscle aches, nausea and fatigue. In the East African Makonde language, chikungunya literally translates to “that which bends up”, referencing the stiffened movements of CHIKV-infected people with joint pain, called arthralgia, that can take months or even years to resolve. It is spread by the bite of an infected Aedes mosquito.
CHIKV predominantly circulates in Africa, Asia and the Indian subcontinent, but has now arrived in the Americas. An outbreak of CHIKV is currently ongoing in the Caribbean. First detected in December 2013 in St Martin, it is now reported as being locally transmitted also in Anguilla, British Virgin Islands, Dominica, Dominican Republic, French Guyana, Guadeloupe, Martinique, St Barthelemy, St Maarten, and St Kitts and Nevis, vectored by the Aedes aegypti mosquito. No role of Aedes albopictus has thus far been reported in transmission from the region. The start of the outbreak at the end of 2013 represented the first records of local transmission in the western hemisphere and as the cases continue to be recorded, there are worries that the disease will become entrenched in the region, impacting residents and tourists alike.
CHIKV had been causing low levels of documented disease until a large outbreak in the Democratic Republic of the Congo in 1999-2000; since then, several severe outbreaks have occurred. In 2005 a widespread outbreak occurred on the Indian Ocean island of Réunion, where an estimated third of the population of the island – over 250,000 people – were infected between March 2005 and April 2006. Two features of this outbreak were unique, the first being that over 200 people are believed to have died due to CHIKV and its complications – a high death toll for a disease rarely known to cause fatalities. Secondly, the strain of virus responsible for this outbreak carried a mutation in one of its protein that has since been shown to contribute to its ability to use Aedes albopictus, the mosquito implicated in this epidemic, as an efficient vector.
In 2007, Italy experienced a CHIKV outbreak vectored by Aedes albopictus. Imported cases had previously been observed in Europe and the USA, but this was the first case of local transmission of what had previously been considered a tropical disease, in a temperate zone. Aedes albopictus has proved highly adaptable as it expands it range to higher latitudes and more temperate climates. As it is firmly established in much of Europe and the United States, these regions now host a competent vector for this debilitating disease.
Like dengue, CHIKV requires Aedes mosquitoes to be present alongside human populations, and so outbreaks are controlled in the same way as dengue outbreaks. Spraying insecticides helps to reduce biting mosquito populations and community campaigns can reduce breeding sites, but the level of control by these methods is inadequate. Here at Oxitec, we have developed products for control of the two principal vectors, Aedes aegypti and Aedes albopictus, which can provide the next level of effective vector control: releases of our Aedes aegypti male mosquitoes against local populations of the former in the Caribbean and Brazil have led to 80-96% reductions of the target vector populations.
We are delighted that Simon Warner has joined the Oxitec team as Chief Scientific Officer. Simon has now taken up the position following Luke Alphey’s decision to focus on earlier stage research at The Pirbright Institute.
Immediately prior to joining Oxitec, Simon was Senior Director of Research and Development Programs and Strategy at Sapphire Energy, based in San Diego, USA. Sapphire Energy is the world leader in making drop-in fuel from algae grown outdoors converting sunlight and CO2 into green crude as a fossil crude oil replacement. Simon has 17 years of global commercial experience in biotechnology research at Syngenta in the United Kingdom and the United States, leading collaborative programmes and delivering biotechnology products in crops for feed and fuel.
Asked what inspired Simon to join Oxitec, Simon replied “It is rare to come across an innovation that has such potential to have a broad impact across many countries in terms of protecting people’s health and environmental sustainability. I was really attracted to the passion in the company to make an impact in these areas and I just wanted to be a part of that.”
In addition to developing and leading R&D programmes, Simon spent some time negotiating agreements to acquire technology to augment the R&D pipeline as well as monetising intellectual property. He holds 15 patents and is a certified Project Management Professional. Simon was the recipient of a David Phillips Fellowship for Biotechnology. He received a BSc in Biochemistry from University College London, and a PhD in plant molecular biology from the University of Leicester.
Panama’s recent field trials approval attracted a number of articles reporting both on the severity of dengue throughout Panama and the potential of Oxitec’s transgenic mosquitoes to improve the situation. Dr Andy McKemey, who leads Oxitec’s field operations, is expertly qualified to talk about working in areas affected by dengue, and spoke to Jon Sopel on BBC World News. In his interview, Andy explained some of the processes involved in field trials, including how we have developed genetically engineered mosquitoes that can be released to reduce the population of dengue-transmitting Aedes aegypti by “well over 95%”.
The BBC also visited our premises near Oxford to discuss how Oxitec can tackle the global dengue problem, as part of a BBC Radio 4 programme looking at UK businesses that are working to address climate change-related issues. Oxitec CEO Hadyn Parry described how dengue has grown as a problem over the last 50 years, and the main vector Aedes aegypti can be found “as far north as Miami, and as far south as Buenos Aires; and pretty much all the way across the world.” Climate change is likely helping the mosquito to spread even further.
We particularly enjoyed a report by the US National Public Radio-broadcast popular science programme, Radiolab. The show describes how mosquitoes plague humanity and why they’re so difficult to control. Reporter David Baker visited Moscamed’s mosquito factory in Brazil to see at first-hand how Oxitec’s technology is being applied to control the dengue-transmitting Aedes aegypti. David discusses with Hadyn how Oxitec mosquitoes are produced, how the genetic marker works, and how the progeny of male mosquitoes cannot survive in the wild: the key to the technology’s success.
In March Hadyn spoke at the US State Department conference ‘Showcasing the Bioeconomy – The Future is Now’ to highlight the potential of Oxitec’s biological control approach in protecting people from mosquito-borne diseases.
While our work in public health is most advanced, we have developed a suite of products in the pipeline for sustainable pest management in agriculture. Hadyn also recently gave a presentation on Oxitec technology at the UK National Farmers Union conference alongside George Freeman MP and Sir Mark Walport, the Government Chief Scientific adviser. Hadyn’s talk generated a lot of interest on Twitter, with farmers tweeting support and questions throughout the day and following the conference. In a subsequent BBC Radio 4 interview on the Farming Today programme, he explained how new biotechnology, like Oxitec’s Olive Fly, can help to deliver environmentally sustainable food production in Europe.
Finally, we’d like to extend our congratulations to Oxitec’s co-founder, Professor Luke Alphey, on winning the BBSRC’s Fostering Innovation awards, 2014. At the award event held on 20th March, Luke won both the social innovator category, and the overall award. These awards recognise Luke’s world-leading research firstly at Oxford University and then Oxitec, in the field of genetic control of insect pests. Visit this link for more details on the award: http://www.bbsrc.ac.uk/news/people-skills-training/2014/140321-n-luke-alphey-wins-fostering-innovation.aspx