Many Insects Resistant To Genetic Manipulation Via CRISPR Editing Tool, Research Finds

Arguments for and against the use of genetic modification techniques in the agricultural and healthcare/disease-prevention sectors typically focus on potential impacts to human health, and/or to wider ecosystems and natural services (a much more important area to watch, in my opinion than human health).

My issue with genetic modification and the use of genetically modified organisms (GMO) in agriculture and disease prevention has always been much simpler though — when you look at the accumulated real-world evidence it’s clear that genetic modification is an oversold sales gimmick.

Certainly there are some things that could be done with genetic modification (whether you consider this to be a good idea or not can be argued either way), but what proponents claim to be possible, and what is actually possible in the real-world, and possible economically for that matter, are quite different.

Case in point, proponents like to claim that common disease vectors, such as mosquitos, can be effectively controlled (wiped out) through the selective introduction of sterility into populations through the use of “gene drives” (genes that spread at a rate of nearly 90%).

New research from Indiana University has revealed something that should have been obvious though, controlling a population of fast-producing and genetically quite varied insects isn’t a simple thing to do.

What the new work, detailed in a paper published in the journal Science Advances, found is that “certain genetic and behavioral qualities in disease-carrying insects, like mosquitoes, make these species resistant to genetic manipulation.”

In other words, on the population and species levels many insects are “actively” resistant to the sorts of genetic modification possible even with the highly accurate and much-vaunted gene-editing tool CRISPR-Cas9.

“We found that small genetic variation within species — as well as many insects’ tendency to inbreed — can seriously impact the effectiveness of attempts to reduce their numbers using CRISPR technology,” stated Michael J Wade, Distinguished Professor of Biology at IU Bloomington. “Although rare, these naturally occurring genetic variants resistant to CRISPR are enough to halt attempts at population control using genetic technology, quickly returning wild populations to their earlier, ‘pre-CRISPR’ numbers.”

So the takeaway of this work is that “costly and time-consuming efforts to introduce genes that could control insect populations — such as a trait that causes female mosquitoes to lay fewer eggs — would disappear in a few months,” as the press release put it.

That’s not say that damage (or benefit, whatever that is considered to be at the time) couldn’t be done, simply that it’s by no means the simple thing that the utopians often pushing the tech have presented it as being.

The press release provides more: “The protective effect of naturally occurring genetic variation is strong enough to overcome the use of ‘gene drives’ based on CRISPR-based technology — unless a gene drive is matched to the genetic background of a specific target population, Wade added. Gene drives refer to genes that spread at a rate of nearly 90% — significantly higher than the normal 50% chance of inherence that occurs in sexually reproducing organisms.

“Wade, an expert in ‘selfish genes’ that function similarly to gene drives due to their ‘super-Darwinian’ ability to rapidly spread throughout a population, teamed up with colleagues at IU — including Gabriel E Zentner, an expert in CRISPR-based genetic tools and assistant professor in the Department of Biology — to explore the effectiveness of CRISPR-based population control in flour beetles, a species estimated to destroy 20% of the world’s grain after harvest.

“The team designed CRISPR-based interventions that targeted three segments in the genome of the flour beetle from four parts of the world: India, Spain, Peru, and Indiana. They then analyzed the DNA of all four varieties of beetle and found naturally occurring variants in the targeted gene sequence, the presence of which would impact the effectiveness of the CRISPR-based technology.

“The analysis revealed genetic variation in all four species at nearly every analyzed DNA segment, including a variance rate as high as 28% in the Peruvian beetles. Significantly, Wade’s statistical analysis found that a genetic variation rate as low as 1% — combined with a rate of inbreeding typical to mosquitos in the wild — was enough to eliminate any CRISPR-based population-control methods in six generations.”

Which effectively means that the potential uses of the tech aren’t what they have been assumed to be.

So, sure, someone can make a glow-in-the-dark bunny, or maybe a weird “look-at-what-I-can-do” hybrid animal, but actually effectively going to war with insect pests and/or microbes, and winning over anything but the extremely short-term? That’s not going to happen. It’s a sales gimmick.

That said, the researchers involved don’t seem to draw the same conclusion, and Wade instead states: “Based on this study, anyone trying to reduce insect populations through this method should conduct a thorough genetic analysis of the target gene region to assess variation rates. This will help predict the effectiveness of the method, as well as provide insight into ways to circumvent natural genetic variation through the use of Cas9 variants with an altered sequence specificity.”

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