Aedes Stegomyia aegypti is a mosquito that can spread dengue
Control mosquitoes like Aedes aegypti and you control Dengue Fever.

If Eden had been created by people, what would the planning debates have looked like? Two months ago, in a remote province of Eastern Malaysia, genetically engineered mosquitoes were released into the wild in a two week experiment aiming to see if wild mosquitoes that infect humans with Dengue Fever might eventually be suppressed or eradicated. The 6000 mutant mosquitoes were the biotechnological brainchildren of Luke Alphey, chief scientific officer of the British biotech company, Oxitec. He has pioneered a technique to inject a suicide gene into a wild insect population in a single generation, causing the pest population to dramatically decline in a bug-ocalypse of dead pupae. The genetic technology, called RIDL, is a fascinating bit of bio-geekery explained in a video below. The politics by which the ecology of the planet might be re-engineered to cause less disease might be even more important for understanding the shape of the future than the tech. This is not the first time that genetically engineered suicide mosquitoes have been released into the wild, and it continues a pattern of acting, then announcing, and then dealing with objections.

Dengue fever is a mosquito born viral disease that resembles a really terrible case of the flu. It infects about 100 million people per year, of whom ~500 thousand get it bad enough to go to the hospital, of whom ~20 thousand die annually. The four serotypes ([1][2][3][4]) have been sequenced already, but there is no cure and no vaccine. Up till now, to control the disease you control the mosquitoes: either clearing out all the standing water in your area (which is very hard in the tropics) or spraying pesticides like crazy. This 2009 video shows Luke Alphey explaining the new RIDL technology’s approach:

Oxitec’s RIDL technology works by almost the same method that the dinosaurs of Jurassic park were controlled. The term RIDL comes from “Release of Insects carrying a Dominant Lethal”. The idea is to create mosquitoes that have two copies of a dominant suicide gene that causes them to die at a specific life stage unless they get a special chemical. You raise thousands, millions, or billions of mutant male mosquitoes in a mutant mosquito factory, getting them past the suicide stage by giving them the special chemical. In Jurassic park, the dinosaurs were deficient in lysine which had to be a regular part of their dino-chow, while Oxitec’s mosquitoes need the antibiotic tetracycline to turn off their suicide genes.

Then, hypothetically, you release the mutant male factory mosquitoes to mate with the female wild mosquitoes so the next generation of children have one copy of the dominant suicide gene but no access to the special chemical. Hopefully the mosquito population crashes, hopefully Dengue fever stops spreading, and hopefully tropical environments become a bit less dangerous to humans. If it works for Dengue, then it might work for other mosquito born illnesses such as malaria, which infects about 225 million people per year, killing over 700 thousand of them.

In The Time Machine, by HG Wells, the world of the future was a biological paradise where every plant and animal in nature had been re-engineered to be pleasing to humans. If we want to Edenform the Earth in this manner then in the long run something like RIDL will be required to clear out the pests… but there’s a catch. RIDL might not work, even in the short term. It seems theoretically unlikely, but given existing experimental evidence, RIDL could actually backfire. RIDL is a more sophisticated version of a pest management technique that’s been around since the 1950’s called SIT, but SIT isn’t used to suppress mosquitoes in part because modeling work done by Alphey himself suggests that SIT attempted without enough mosquitoes can paradoxically cause more adult mosquitoes to survive into adulthood because they aren’t overcrowded during their larval stage. Biological systems have a tendency to throw unintuitive curveballs like this, and if one paradox can turn up in a decades old technique, why couldn’t some other factor throw a spanner into RIDL’s chances of success? RIDL might be a technology that ushers in a new era of health for the developing world, but if it backfires, it won’t be Luke Alphey who gets sick: it will be Malaysians living near the test sites. Do Malaysians get a say in the tests? Through what institutions?

This is where the politics comes in. The Malaysian government released the mutants from December 21st to January 5th, but the fact of the release was only announced by the Malaysian Institute for Medical Research on January 28th. Even as the release was happening, protest letters were being registered in local media by prominent Malays, including members of parliament and the president of the Consumers Association of Penang. And back in Oxitec’s home turf the NGO GeneWatch was releasing scientific comments criticizing the risk assessments offered by Oxitec.

Oxitec’s projects seem to have a habit of being politically complicated. The only previous release of their mutant mosquitoes was in the British ruled Cayman Islands, and the educational video about the subject (shown below) conveniently fails to mention that the mosquitoes involved have been genetically engineered. The Cayman release, though successful in reducing the local mosquito population by 80%, wasn’t widely publicized until long after it had happened. An attempt to work with India became complicated before a release could occur.

Opponents of the Malaysian release raised a host of scientific worries, some based in generic fears of genetic engineering, and others relatively concrete and specific. One concrete fear raised by GeneWatch is that RIDL might eventually be used to successfully suppress Aedes aegypti, which spreads Dengue, thereby opening up a niche that might be filled with a non-targetedd mosquito like Aedes albopictus, which also lives in Eastern Malaysia and also spreads Dengue. Albopictus might not take over the niche, and even if it did it might be less dangerous, but the likelihood of this or similar problems has never been formally ruled out. Another, more immediate risk raised in GeneWatch’s comments is that about 3% of the released mosquitoes are accidentally female and about 3% of the wild suicidal generation don’t actually die. If the suicide genes persist in the wild, the local population might evolve resistance that makes future management more difficult. Countering this last point, the Malaysian government asserts that all the experimental mosquitoes were killed by spraying at the end of the experiment.

Map of the world showing the extent of both Aedes aegypti and Dengue.
Evolving in Africa, Aedes aegyptis was globalized by 2006. Red regions have the mosquito and Dengue, blue regions only the insect.

The big hope in all this is that Oxitec’s approach to mosquito control could be hugely important for diseases in the developing world, and RIDL is the logical cautious next step in this area. Back in 2003, researchers like Mark Benedict and Alan Robinson were already proposing that the safest sort of genes to practice injecting into natural populations would be genes that caused the death of the next generation and were therefore inherently self limiting. A mosquito strain reported in 2010 that was incapable of transmitting malaria at all, but that sort of gene would need to be injected into a population and sustained over time, which necessarily involves more things that could go wrong. RIDL is a conservative first step in this area because it isn’t intended to persist in the environment. If it works correctly, each application is a one time shot. If humanity is going to practice injecting new genes into the natural world, RIDL is the sort of thing to practice with.

While RIDL is a first step, it is by no means the first GMO released or in development. Genetically engineered agricultural crops have been sending pollen into the natural world for 15 years and even other animals, like enviropigs and genetically modified salmon, are in the research pipeline. The big difference with Oxitec’s RIDL mosquitoes is three fold. First, this is a radically international process. Aeges aegypti evolved in Africa but has migrated around the planet from Florida to Australia. If Oxitec’s mosquitoes aren’t appreciated in one country the company can simply try next door. Second, genetically modified animals are now being released into the natural environment with the intent to change the natural environment itself rather than simply for agricultural or chemical manufacturing purposes. Third, this is happening through government regulated channels, but it raises a host of novel political issues that will probably come up again and again in the future. On many levels, Oxitec’s RIDL mosquitos are a taste of what’s coming.

Part of the promise of exponentially improving technology is the expectation that more and more problems will be solved faster and faster, but some problems require collective action. Sometimes each person can buy their own gadget, but other times technology has to be adopted in a single jump by entire communities. Ecology engineering is the second kind of technology. If Dengue has been controlled by 2018, it won’t just be a technical triumph, it will also be a political marvel.

[image credits: Muhammad Mahdi Karim via WikiCommons, Agricultural Research Service of the US Dept of Agriculture]

[sources: Time, Discover, Daily Mail, NCBI]