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When the Pest Becomes the Pesticide: Genetically Reprogramming Mosquitoes, Moths, and More

It’s hard to imagine what a world would be like without mosquitoes, ticks, beetles, termites, and other pest insects that have plagued human health, agriculture, and economy for as long as we can remember.  But with the innovation of genetically-modified pests and gene drives, someday soon a pest-free environment may no longer be the stuff of imagination.

Case in point: biotechnology company Oxitec, the uncontested industry leader in gene-based pest control, recently announced that it was moving forward with their second major project for combating one of the most intractable pests in agriculture: the diamondback moth.  The Intrexon subsidiary rolled out their pilot program for combating the Aedes aegypti mosquito in several countries over the past year and is now broadening its horizons to include the destructive moth.

Thus far, Oxitec’s two targets—the mosquito and the moth—impact human health in very significant ways.  Aedes aegypti is the carrier of Zika virus, dengue fever, and yellow fever and the diamondback moth causes an estimated $5 billion of damage annually to crops in the U.S. alone.  These high-stakes species (among others) are ones that we’ve been battling with chemical warfare for ages, but Oxitec is coming at them from a fresh angle.  In both cases, the company is introducing GM bugs possessing genes that are designed to sabotage entire populations of pests, turning their own genes against them in an operation that ultimately leads to self-destruction—no pesticides necessary. 

So far, it appears to be working. Oxitec reports that trials of its Friendly™ Aedes project have resulted in a greater than 90% reduction in the disease-carrying mosquito population at sites in Brazil, Piracicaba, and the Cayman Islands.  Earlier this year, new trials were initiated in India and other area such as  Brazil.  The success of Oxitec’s genetic saboteurs spells a lot of promise for its up-and-coming moth that is based on the same principles.  But at the same time, other researchers are rapidly developing a technique for confronting pest species that could prove even more successful than Oxitec’s approach.  That technique is known as a gene drive.

What is a gene drive, and how does it work?

A gene drive describes a genetic element that is spread throughout a population over several generations by being passed from parents to offspring at an abnormally high rate.

Gene drives defy normal patterns of inheritance and evolution.  When organisms with two sets of chromosomes mate and reproduce, each parent will only pass down one chromosome to their offspring, meaning there is a 50% chance that each parental chromosome will be inherited.  Gene drives, however, can greatly increase the probability that one chromosome’s genes will be inherited over the other, sometimes causing the probability of inheritance to near 100%.  Over just a few generations, this causes the gene and its trait to appear in the population much more frequently than normal laws of inheritance and genetics would dictate.

To further turn what we know about evolution on its head, gene drives can function this way even when the gene of interest is harmful to an organism’s ability to survive and reproduce.  Thus, a gene drive can be designed that will shut down or sabotage certain essential genetic circuits that normally allow a species to flourish.  

What’s the difference between Oxitec’s approach and a gene drive?

The approach that Oxitec is undertaking, while quite effective, is limited in the fact that it is not truly a gene drive and lasts only for one generation.  Here’s how the Oxitec process works: Oxitec genetically alters male mosquitoes to include a gene that causes the mosquito to die before reaching maturity unless provided with a chemical anecdote.  Lab-made males are supplied the anecdote so that they can survive long enough to be released into a wild population and mate with its females, displacing the mating potential of wild males.  The offspring between a GM Oxitec male and a wild female will contain the self-destruct gene but, unlike their male parent, they won’t be exposed to the anecdote.  Those offspring will die before reaching adulthood.  As more and more waves of GM mosquitoes are released to mate with the wild mosquitoes, a steep decline is seen in the local mosquito population and, in conjunction, a decline in mosquito-borne illnesses.

Oxitec’s genetically modified diamondback moth is engineered in much the same way, although the resulting impact will not be on human illness but rather crop loss.  The diamondback moth is one of the trickiest crop pests to control because its short reproductive cycle causes it to develop resistance to chemical insecticides very quickly (the moths are currently resistant to 95 pesticides and counting).The Oxitec moth represents an unprecedented approach to sidestepping chemical resistance in crop pests and is currently being considered by the USDA for a trial run at a 10-acre plot in New York.

But no matter how well the moths perform, they will still encounter the same problem as Oxitec’s flagship mosquito: that is, the necessity for re-release.  The mosquitos’ self-destruct gene means that the pest-controlling effect only lasts for one round of mating before the technology is exhausted.  Many successive batches of Oxitec’s mosquitoes must be released in order to achieve the gigantic population reductions that the company has reported—and all those mosquitoes represent a lot of work, as well as a lot of money.  The same goes for the company’s GM diamondback moth.

Gene drives, on the other hand, could in theory stop a population in its tracks after a single event releasing one group of GM mosquitoes.  That’s because the effect of a gene drive lasts longer than just one round of mating and over time will cause a gene to be propagated to all descendants of the organisms that carry it.  For example, a research team led by Kevin Esvelt at MIT is currently working to develop a gene drive that will make Aedes aegypti resistant to viruses like Zika, dengue, and yellow fever.  In principle, by introducing a few mosquitoes containing viral resistance genes, within a few generations all mosquitoes in the local population will contain these genes and be equally resistant to these viruses.  And if the mosquitoes can’t catch these diseases—neither can we.

The extraordinary power of genetic pest control

In this way, gene drives represent a more powerful and lasting strategy for managing and controlling populations of pest species from the inside out.  Gene drives mean that the genetic manipulation of entire populations—once considered impossible—can potentially be accomplished with the release of a single group of genetically modified organisms.

But like any technology with the power to dramatically improve our world, gene drives also have the power to be devastating.  Deployment of gene drives in the wild has the potential to impact the genetic profile not only local populations of pests but entire ecosystems, possibility to the extent of completely eradicating particular genes within a species. It is very difficult to predict what kind of downstream unintended effects this kind of universal manipulation will have on a species, not to mention the species that interact with it.  Furthermore, as the realities of global climate change take hold, it will also become difficult to predict how the ranges of different species will change and, in turn, how a gene drive will propagate throughout different ecosystems.

For these reasons, not everyone believes that the power that comes with gene drives is something that should be unleashed upon the world.  Some scientists and activists have called for a temporary moratorium on gene drive research, while others have gone as far as to call for a complete and permanent ban.

But at least one person is championing a more tempered approach to gene drives, maintaining that research on them should proceed, but decisions about their implementation should not rest solely with scientists.That person is MIT’s Kevin Esvelt, the very same mastermind of the earlier-mentioned viral-resistant mosquitoes.  Esvelt believes that scientists must partner with community members and take their input seriously when weighing the ethical consequences of pursuing wild-release gene drive technologies.  After all, these community members are the ones who will be living among gene-driven populations of various pests and are as much a part of the affected ecosystem as the pests themselves.  If any negative externalities of a gene drive do emerge, it is community members who will be affected and therefore, according to Esvelt, these members must be an essential part of the decision making process.  The link below contains a video of Kevin Esvelt discussing this issue at the Media Lab’s 30th anniversary event in October 2016.

This sort of approach to public outreach in the scientific enterprise could be considered unprecedented—but then, so are gene drives in what they promise to do for the world and how they promise to do it.  Extraordinary technologies call for extraordinary measures.

Until those measures are established, the path to gene-based pest control is being paved by more limited but less precarious technologies like Oxitec’s GM mosquitos and moths.  It may not yet be clear what role gene drives will play in our imagined pest-free future, but with so many teams now tackling the practical and ethical dimensions of gene-based pest control there’s no doubt that this future is becoming less difficult to envision all the time.

For discussions with key thought-leaders on hot topics like these, join us for SynBioBeta San Francisco 2017 in October.  

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Christine Stevenson

Christine Stevenson is a freelance science writer and adjunct professor of biology at the Maricopa Community Colleges in the Phoenix metropolitan area. She holds an M.S. in Biology from Arizona State University and has a background in both wet lab research and venture capital consulting. She lives in Tempe, AZ with her dogs, cats, chickens, and goat.

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