The science of editing a mosquito’s genetic make-up
The backyards of Cairns and Townsville may seem an unlikely setting for a biological battlefield. But as the number of infections from Zika and dengue fever swells, the efforts made in these ordinary households have gained global attention – and could prove a turning point in attempts to arrest the spread of mosquito-borne viruses.
The Zika virus, which is closely related to dengue, yellow fever and chikungunya, has commanded much media spotlight in recent months. The telltale signs of infection – an enduring malaise, joint pains, headaches and an eruptive fever – are said to be much less debilitating than dengue, which is known as “breakbone fever” for good reason. Yet a degree of malignance belies Zika’s apparent mildness. The increase in Zika infections in Brazil has seemingly been accompanied by a rising prevalence of microcephaly among newborns in that same country – a neurological defect marked by an abnormally shrunken head – which has heightened fears about the far-reaching complications and costs for mothers. Although there has not yet been scientific confirmation of a link between the Zika virus and congenital defects, the mere suggestion of correlation has led the World Health Organisation to declare the outbreak a “public health emergency of international concern”.
So far, 6000 people in Cairns and Townsville have signed up to breed Aedes aegypti mosquitoes – the primary vector that transmits Zika, dengue and chikungunya – in noodle box-sized containers in their gardens as part of a global, non-profit collaborative project run by Eliminate Dengue, led by Monash University professor Scott O’Neill. Given that both towns have been vulnerable to dengue outbreaks in the past, trying to ward off pestilence by breeding more pests seems to defy logic. But the mosquitoes being bred aren’t your average bloodsucker: they’ve been deliberately infected with bacteria that neuter their ability to pass on the virus during the mating process.
Wolbachia is a naturally occurring bacteria commonly found in insects around the world, but it is absent in the A. aegypti mosquito. O’Neill and his team extracted Wolbachia from fruit flies and used microscopic syringes to introduce it into mosquito eggs. The genetic material of the mosquito remains untouched. Once a mosquito is infected with Wolbachia, it passes it on to its offspring, so the process only needs to be conducted once – unlike, say, insecticides, which would need to be applied multiple times. So far, CSIRO’s risk analysis of Eliminate Dengue’s work with Wolbachia has shown the bacteria do not pose a danger to humans or the surrounding environment.
O’Neill’s trials found that mosquitoes infected with the Wolbachia bacteria are less likely to transmit a range of viruses, including Zika and other mosquito-borne afflictions. “In those areas where Wolbachia gets to a high level in the mosquito population, we haven’t seen any dengue transmission in those communities since Wolbachia has been deployed,” he says. The intervention isn’t about trying to kill the mosquitoes, he says, but about “trying to make them harmless”. At least one Wolbachia strain has been found to shorten mosquito life span, which O’Neill says could have a “large impact” on disease transmission.
The nature of Eliminate Dengue’s project has required deep consultation with local communities since trials were initiated five years ago. It has so far garnered strong support among residents, and has also been introduced at schools, where students are encouraged to take the mosquitoes home and observe their behaviour. Similar, small-scale trials are also being undertaken by researchers in Indonesia, Vietnam, Brazil and Colombia. “Community engagement is really fundamental to our success,” O’Neill says. “We needed time to build authentic relationships with communities.” It is an acknowledgment that a mixed legacy of biological control weighs on public sentiment.
Meanwhile, in the US, a team at the Massachusetts Institute of Technology led by Kevin Esvelt is taking a radically different, and perhaps more controversial, direction in combating Zika and other pest-borne viruses. Esvelt’s team has proposed using gene drives – altering the DNA of a particular species to affect its entire population – to drastically reduce the mosquito populations. If its gene drive technology is deployed, it could strike these disease-carrying mosquitoes from existence, potentially eliminating Zika, malaria and other pest-borne diseases in a short space of time. But editing a mosquito’s genetic make-up to sterilise the species could be fraught with unintended consequences. It’s never been done before. “The gene drive is not like other technologies,” Esvelt says. “It acts on the ecosystem and therefore on the community. There is no even proxy for consent in the form of requiring mass adoption in the marketplace before you start seeing effects.” He says that it would be unethical to deploy a gene drive without broad public support.
Sometimes scientific evaluations of risk and ethics can sharply contrast with that of the general public. Esvelt’s abiding fear “is that we will fail to deal with this technology with wisdom and humility and it will consequently widen the divide between scientists and society”. Discussions about genetic modification and biological control reliably reactivate society’s ingrained anxieties about what could happen if science goes “too far”, and how our personal agency – our humanity – might be affected. Films such as Jurassic Park and Gattaca are cautionary tales not only about the dangers of meddling with nature, but of the perils of disciplinary overreach.
The debate about the ethics of genetic modification can lack nuance: the schism between “nature” and “the artificial” is prone to exaggeration. But such measures arouse suspicions because the effects on ecological systems and biodiversity can be unpredictable. Sometimes the cure can be worse than the disease. Cane toads, which were introduced into Australia by the then Bureau of Sugar Experiment Stations in 1935, were brought in to tackle the scourge of the cane beetle, but became an out-of-control pest – a natural weapon of mass destruction. Recent research reported in New Scientist magazine suggested the endurance of cane toads is producing unexpected environmental effects, such as a boost in the population of the crimson finch as a result of the toads eating the bird’s predators, the Mitchell’s and Mertens’ water monitor lizards. This illustrates what prominent zoologist Robert Paine termed a “trophic cascade”: even the slightest tinkering to an intricately woven ecosystem can yield a wholly unanticipated outcome.
British biotech firm Oxitec has been awaiting Food and Drug Administration approval in the US for four years to release its bioengineered A. aegypti mosquitoes into the wild in the Florida Keys. Unlike gene drive technology, though with a similar result, Oxitec injects a substance into mosquito eggs that delivers a lethal protein to the developing mosquitoes. These modified mosquitoes survive the protein by being fed a diet of tetracycline antibiotics in the lab, but their untreated offspring succumb to its fatal effects and expire. In two Brazilian villages, populations of A. aegypti have drastically declined by 60 to 70 per cent using this method, according to a University of Sao Paulo biologist quoted in The New York Times; the company claims an average reduction rate of 90 per cent. By comparison, pesticides have an average reduction rate of 30 to 50 per cent. But the initiative has been met with steadfast resistance from residents of the Key Haven community, who feel they are being treated as little more than lab rats in an opaque scientific experiment. More than 160,000 have already signed a Change.org petition to stop the release of Oxitec’s mosquitoes, which are referred to as “mutants” in the petition’s preamble.
None of this surprises Esvelt, who harbours deep misgivings about the way scientific research projects are developed and subsequently commercialised. “Our society does not develop technology in a way that I would consider to be wise,” he says. “It is done largely in secret by people who tend not to request advice from others as to what concerns people might have, how things might go wrong, and how those concerns might be addressed in the development cycle.”
Part of Oxitec’s image problem is its motive for profit, which Esvelt and his team, and O’Neill and his academic colleagues, do not share. Both Esvelt and O’Neill seem acutely cognisant of the challenge and necessity of building trust and empathy among the community, an ethos that is sometimes given short shrift in favour of theoretically elegant goals or commercial imperatives. They recognise there’s a difference between being subject to science and being a part of it.
Meanwhile, researchers will continue to work on determining how dangerous a threat the Zika virus is, and what should be done to reduce its spread, along with dengue, yellow fever and chikungunya.
This article was first published in the print edition of The Saturday Paper on Mar 12, 2016 as "Mosquito host". Subscribe here.