Operation exterminate mosquitoes

April 2012
Female Aedes aegypti mosquito
By James Gathany [Public domain], via Wikimedia Commons
'Dengue fever' is an illness caused by a virus which is transmitted from person to person by biting female mosquitoes belonging to the species Aedes aegypti.

Infection can lead to a full continuum of disease: the symptoms are 'flu-like, but are rarely fatal and up to half of cases are asymptomatic; Dengue Shock Syndrome and Dengue Hemorrhagic Fever are potentially life-threatening; the latter is seen most often in children and causes death in 5% of cases.

The focus of control of dengue is to eliminate the mosquitoes which carry the virus and so break the cycle.

To this end a UK biotech company, 'Oxitec' (see below), has created self-destructing GM mozzies.




Oxitec

Oxitec was spun out of Oxford University in 2002.

The Company has received funding from the Wellcome Trust (a UK charity) and from the UK Government. It has secured a £2.25 million loan from a US multi-millionaire.

Advisors to Oxitec investors include a former Government Science Minister and a former Royal Society President.



Oxitec has genetically transformed its mosquitoes to generate a novel enzyme which binds the anti-biotic, tetracycline. In the absence of tetracycline, the larval form of the insects produces so much of the GM enzyme that they kill themselves. In the presence of tetracycline, the insects can grow and reproduce normally. A fluorescent marker gene has also been inserted.

This clever mechanism allows the mosquitoes to be bred in the laboratory (in the presence of tetracycline to keep them alive) in huge numbers. The males and females can then be separated from each other by machine because they're different sizes, and the males only are released into the area to be cleared. When the males mate with wild females, the resulting wild offspring haven't any tetracycline to keep them alive and they self-destruct.

Besides acting to prevent female mosquitoes from successfully producing a new generation, the GM grubs survive for long enough to usefully compete with their non-GM cousins for vital environmental resources.

Preliminary computer modelling indicated that, by maintaining a ratio of six male GM mosquitoes to one female wild mosquito over a period of just over a year, a population of Aedes aegypti could be eradicated. Oxitec has suggested a stockpile of between 100 million and 1 billion GM mosquitoes should be created to complete any given mozzie-elimination project.

Environmental trials of the Oxitec mosquitoes are already underway:
  • During 2009-2010, a small release followed by a release of 3 million GM mosquitoes was trialled in a small town in the Cayman Islands (the Caymans have been a British Overseas Territory with their own constitution since 2009).
  • During 2010, 6,000 GM mosquitoes were released on an uninhabited area in Malaysia. A larger release in a populated area is planned.
  • During 2011, 33,000 GM mosquitoes were released in cities in North East Brazil.
  • Other proposed trial sites include Panama, India, Singapore, Thailand, Vietnam, the Philippines, Costa Rica, and Trinidad &Tobago.
The outcome of the largest trial was reported in very positive terms by the science journal, Nature: “the controlled release of male mosquitoes, genetically engineered to be sterile has successfully wiped out dengue fever in a town of around 3,000 people in Grand Cayman”. The author of this article seems a little confused: the released mozzies weren't sterile, and even Oxitec contradicted the hyperbole by announcing the test had resulted in a reduction in the Aedes aegypti population of 80%.

The next trial planned is a two-month study scheduled for Florida and should have happened in early 2012 with a release of 5-10,000 GM mosquitoes over two weeks.

However, all has not gone well in the US. There have been regulatory challenges, and civil society groups, now alerted, have called for an immediate halt to field trials and a re-assessment of the risks posed by the technology.

The immediate problem in America came from its failure to put in place regulations specifically for GMOs. As its government clings to the notion that existing laws can be used to control the products of gene-technology, the US is finding that GM mosquitoes fall through all their existing nets: they don't impinge on agriculture, they're not a disease, they're not a food nor a pollutant, and they won't be released in areas with important wildlife.

It seems likely that, when all the US agencies have finished passing this GM buck, the novel enzyme produced by the mozzies will become a “drug” and be regulated by the Food and Drug Administration, like the super-salmon which also got stuck in a regulatory limbo (see THE GM SALMON SAGA - February 2012 ).

Other legal questions are being asked about the trans-boundary movement of the mosquito eggs produced in the UK. The Cartagena Protocol on Biosafety and other international agreements have specified procedures on the export and import of organisms. The UK is a party to these treaties, so the Cayman Islands could be used as a laboratory for experimental GM insect releases with no more than a local permit from the Cayman Island agriculture department and a notification of the egg shipment. The US is not a party to the Cartagena Protocol, so although Oxitec (in the UK) will be required to provide an environmental assessment before shipment, it's unclear which US authority, if any, will receive, review, consult and publish this.

Then there are ethical concerns over the apparent secrecy surrounding the previous trials:
  • A Cayman Island researcher involved in the GM release was adamant that, besides extensive government involvement, there had been a newspaper article and public consultation within the Islands. However, the only public information uncovered by GeneWatch investigators was a video entitled “MRCU* sterile mosquitoes” on the Cayman Island Government Information Service website after the release had taken place. (*Mosquito Research and Control Unit)
  • In Malaysia, the public weren't informed of the trial until a month after the release had started, and a press report that the release had been delayed appeared after the trials had begun.
  • Information of any kind on the Brazil release is very scant.
This leaves the lack of consent from the people who are within the experimental zone as a major issue.

Since mosquitoes are in direct contact with humans, externally on their skin and internally in their blood stream (and could be inadvertently consumed or inhaled), ethical principles for research involving human subjects should have applied. These include providing the subjects with information on:
  • the aims, methods, funding and conflicts of interest of the experiment
  • the anticipated benefits, potential risks, and discomforts involved in the experiment
  • their right to refuse to participate or to withdraw consent to participate at any time.
Besides all the legal and ethical issues, there are solid scientific concerns and serious technical weaknesses surrounding the GM Aedes aegypti project. For example:
  • The sorting of males from females is 99.5% efficient. This means that 0.5% of releases are GM biting females: 0.5% of repeated waves of tens of thousands of mosquitoes amounts to a significant level of contamination. The GM females are able to transmit the novel protein and the novel DNA construct directly into human blood.
  • Unaccountably, 3-4% of the larval GM mosquitoes manage to grow to adulthood without exposure to tetracycline. If this is due to transgene instability, the population of GM biting adults could escalate over time.
  • Many areas in the environment are contaminated by tetracycline, which is extensively used in intensive livestock operations. For example, levels of the antibiotic in sewage is enough to generate 15% adult GM mosquitoes.
  • The novel DNA construct was inserted into the mosquitoes using a 'jumping gene' which aggressively invades the genome. Such mobile elements can continue to move around the original host, and can transfer into other organisms. As the Institute of Science in Society puts it, putting jumping genes into a mosquito is “to give them wings, as well as sharp mouthparts for efficient delivery to all plants and animals and their viruses.”
  • Any area 'cleared' of Aedes aegypti by GM competition, will soon be re-invaded by wild-types from surrounding areas. Worse, the gap left by the decimation of dengue-fever carrying insects might be filled by something much worse, such as the Asian Tiger mosquito which transmits more diseases than Aedes aegypti and is one of the world's most invasive species.
  • The most fundamental problem with the scheme is scientific: there's no correlation between Aedes aegypti population levels and the incidence of dengue fever in humans. These mozzies preferentially feed off humans so that even a very small population of the insects will transmit the disease effectively.
Given that keeping down a mosquito population using GM self-destruct insects will require large repeated releases in perpetuity, the problems identified above will eventually unfold in some form.

GeneWatch has highlighted that Oxitec is running at a loss of £1.7 million a year which will continue until its GM mosquitoes are successfully marketed. The £2.25 million private loan is due to be repaid by 2013. The Company's business model assumes that developing countries will lock themselves into ongoing payments for GM mosquito releases. The bottom line is a huge financial pressure on Oxitec to make the product 'succeed'.

OUR COMMENT

Despite the Company's prestigious background, here seems little incentive for Oxitec to be honest about the ethics, efficacy or safety of its product.

The Institute of Science in Society has pointed out that scientists not obsessed by GM solutions have come up with another way to combat dengue fever. Their research involves a natural bacterium which stops the dengue virus from multiplying inside its mosquito host. The bacterium shortens the life-span of the mosquitoes, but not enough to wipe them out, and also protects against other mosquito-transmitted diseases. By releasing mosquitoes infected with this bacterium into an area, the protection spreads quickly, naturally and permanently through the whole population.

For more on the non-GM approach to biological control of mosquito-born disease, check out


SOURCES
  • Eric Hoffman, Genetically engineered mosquitoes in the U. S., Friends of the Earth Brief, December 2011
  • Oxitec's genetically-modified mosquitoes: in the public interest? GeneWatch Briefing, December 2010
  • Can GM Mosquitoes Eradicate Dengue Fever? Institute of Science in Society Report 8.12.10
  • British Overseas Territory used as private lab for GM mosquito company, GeneWatch UK, 14.12.10
  • Katherine Nightingale, GM mosquito wild release takes campaigners by surprise, Science and Development Network, 11.11.10
  • GM mosquitoes' survival rate concealed, Friends of the Earth News Release, 12.01.12
  • Helen Wallace, GM mosquitoes - threat or friend? Public Service Europe, 12.01.12
  • Wenonah Hunter, Guinea pigs for mosquitoes? Sun-Sentinel (Florida), 5.12.11
  • jControversial release of genetically engineered mosquitoes delayed, Friends of the Earth News release, 2.01.12

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