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The Future of Pest Control Lies Within (the Pest)

Credit: Vera Kuttelvaserova/Adobe

Credit: Vera Kuttelvaserova/Adobe

By Alexandre Fournier-Level

Gene drives could improve global food security by turning pest biology against itself.

Between 1845 and 1847, the potato blight (Phytophtora infestans) ravaged Ireland, where potato was the staple crop, causing the death of more than a million people and forcing the emigration of another two million. The Great Famine added another hallmark to the long list of plagues humanity has faced, along with the plagues of Egypt in the Bible or locust plagues during the Yuan and Ming dynasties.

The Green Revolution over the first half of the 20th century owed itself to the widespread application of chemistry in agriculture. It can be seen as the milestone after which we ceased to fear agricultural diseases as life-threatening plagues. But for how long will this remain so?

Two recent and dramatic events that went relatively unnoticed are a reminder that food security is fragile and that we are more vulnerable to disease and pest outbreaks than we probably think. In 2007 Ug99, an extremely virulent strain of black stem rust (Puccinia graminicola), started infesting East African wheat fields and ultimately extended to the Middle East. In 2016, a wheat blast caused by the fungi Magnaporthe oryzae originating from South America spread to Bangladesh, somehow jumping from rice to wheat.

The extreme vulnerability of modern agriculture stems from several factors, including the narrow gene pool of the crop (which was already the main vulnerability during the Great Famine), biosecurity issues arising from the increase in global trade, the current state of scientific knowledge and economic rationale that tend to favour short-term chemical answers to long-term biological problems.

Pesticides are increasingly blamed for polluting ecosystems, but these chemicals are our first line of defence. However, their efficacy is threatened: the first mass-produced herbicide 2,4-D, released in the 1950s, remained effective for several decades before resistance developed, and we are now experiencing a situation where herbicide efficacy only lasts a decade or two. New pesticides are being designed but we are running out of options. In order to diversify our defence arsenal, biological controls have been deployed with some success, such as ladybugs preying upon aphids or wasps parasitising the eggs of pest moths.

However, current biological methods of pest control suffer many intrinsic limitations. There needs to be a suitable predator, parasite or pathogen of the pest that can be deployed within the cropping environment. Furthermore, the consequence of the biological control escaping the crop to become an invasive pest is also a possibility. Think of the dreadful cane toad, which has been useless at controlling grey-backed beetles but has invaded and changed the food webs of most of tropical Australia.

While there might not always be a natural enemy of the pest available to develop a biological control strategy, every organism needs specific genes to develop, so why not exploit this vulnerability and base the control on the pest’s own genome?

Using the pest’s very own biological vulnerability at the molecular level is not a new concept, but it would be substantially enabled by two key things. First, we need a system that brings genetic engineering tools inside the pest cell. Second, we need a way for the engineered gene to diffuse across the pest population.

This is now possible through the development of synthetic gene drives using CRISPR/Cas9 molecular engineering technology. This technique represents an unprecedented possibility of bringing a genetic conflict to a noxious organism simply through the introduction of a single non-native gene, the Cas9 endonuclease gene, into the genome of the target pest. This is in stark contrast to other biological control approaches that introduce new species into the ecosystem.

In theory there is no limitation to which gene or genes can be the target of a gene drive. The targeted gene can be simply deleted (the most simple and straightforward application), added or edited. The gene drive will then convert the other gene copy or allele present on the sister chromosome into the engineered form of the gene, and multiply it through the population.

A gene drive can have different objectives, from simply amending the genetic make-up of a population (e.g. by introducing susceptibility to a pesticide or a reproductive incompatibility) to the extinction of a target species (a “crash drive”). In terms of ethics, designing a gene drive to restore susceptibility to a pesticide for which the pest has developed resistance seems more acceptable than seeking its extinction.

Nevertheless, the complexity of biological ecosystems and our lack of understanding should make us very humble: numerous things could go wrong when using a gene drive for pest control, and we will first need to close the knowledge gap before considering any field release.

Agricultural systems have all the features that could lead to the rapid diffusion of an escaping biological agent: massive areas with high densities of a single species in favourable environmental conditions and connected to other agricultural zones around the world. This provides the perfect trigger for a demographic explosion by an organism capable of exploiting the agrosystem.

So will any genetically engineered species released in an open field necessarily escape human control? While the purpose of a gene drive is to spread, escape could be limited if the means of control has been carefully anticipated. Since the activity of a gene drive strictly depends on the presence of the Cas9 endonuclease gene, it is possible to introduce small guide RNA sequences (sgRNAs) aimed at deleting the Cas9 gene itself. Once Cas9 is expelled from the genome of the target species, there is no risk of the gene drive multiplying out of control.

For this strategy to be effective, the initial gene drive must only be effective for a certain period before the second, anti-Cas9 sgRNA disrupts the gene drive’s activity. This remains a challenge, but progress in our understanding of gene regulation, such as epigenetic modification, may soon allow the delay of anti-Cas9 activity relative to the primary drive.

However carefully designed the gene drive is, it cannot be ruled out that a molecular error will be introduced, and its consequences are difficult to anticipate. We typically should remind ourselves that the abundance of genetic diversity present in the living world is entirely the result of errors and malfunction of the cellular machinery, and this imperfection is the driver of evolution.

Nevertheless, gene drives have a critical advantage over biological control using another species: since the arena lies within the genome of the pest species, there is no risk of introducing a new pest. An optimistic standpoint would just consider that, at worst, the gene drive may not solve the initial problem. The possibility of the gene drive escaping through hybridisation remains to be considered, but fortunately most pests are not native and are rarely at risk of hybridising with sister species.

As a result of our over-reliance on a few all-purpose pesticides, pests have become resistant and the dose used has needed to be increased to the point where most fields and ecosystems have become highly polluted. This is not the fault of the chemical industry, and even less the farmers; it is the fault of applying simple solutions to complex problems.

Gene drive technology will create new opportunities and will be informed by emerging models where biological interactions are considered down to the molecular level. Each pest issue could be tackled in the most specific possible way, without harm to other species. We may no longer need to have fixed varieties of crops and breeds of livestock, but instead could use locally adapted, better-suited plant and animal populations in which we occasionally introduce a new beneficial copy of a gene that will diffuse through a gene drive. This is the way forward to reconcile productive agriculture and maintenance of biological diversity.

Dr Alexandre Fournier-Level is a Lecturer at The University of Melbourne’s School of Biosciences.