EPA fast-tracking of gene-altering pesticide sparks concerns

US regulators are fast-tracking a novel, gene-altering insecticide in an unusual move that would greenlight the product for three years of commercial use before a standard testing period is completed.

Calantha, a product of the company GreenLight Biosciences, contains the active ingredient ledprona, which uses a mechanism called RNA interference (RNAi) to kill the Colorado potato beetle, a notorious pest, by turning off genes it needs to survive. Calantha would be the first pesticide spray using RNAi, though the technology has been genetically engineered into some corn plants to protect them from the corn rootworms, and RNAi has a history of use in medical therapeutics and vaccines.

The Environmental Protection Agency (EPA) just granted GreenLight Biosciences an Experimental Use Permit (EUP) in May, giving the company two years to gather and assess data from use of the new product in limited test plots. But now the new pesticide could be widely sprayed on potato crops around the country as early as this spring.

Critics fear that the new pesticide is being rushed to market without sufficient data to demonstrate that it is safe for human health and the environment. They also question whether it will be effective.

“It’s a huge precedent-setter,” said Michael Hansen, a senior scientist at Consumer Reports. “This is a new form of pesticide which has never been on the market before. When this is a new class [of pesticide], you shouldn’t be cutting corners.”

The EPA said Friday that it is extending the public comment period for ledprona following a request from the environmental group Friends of the Earth. The deadline for the comment period, which was scheduled to end October 13, has been moved to October 30.

Unintended consequences

Agrichemical companies applaud gene-silencing pesticides as a promising solution to the problem of pest resistance and an answer to consumers’ call for pesticide residue-free products. 

In 2021, the US Department of Agriculture wrote a letter to the EPA strongly encouraging the agency to authorize ledprona for experimental use, writing that it “could displace some broad-spectrum insecticide usage” and could help potato growers manage the invasive insect.

Multiple studies have “confirmed” that the product has no harmful effect on “people, pollinators, birds, fish or other non-target organisms,” said a spokesperson for GreenLight Biosciences. “Additionally, unlike the commercial chemical pesticides commonly used to control Colorado Potato Beetle, Calantha leaves no detectable residues on food, soil, water or in the atmosphere,” the spokesperson said.

Still, opponents fear embracing this biotech alternative to chemical pesticides without carefully assessing risks could simply create new problems. Gene-silencing pesticides, which large companies including Bayer, BASF, and Syngenta are also developing, could potentially harm off-target species and jeopardize farmers’ health, critics argue. 

“We can’t assume that because a technology is biological and not chemical that it is necessarily going to be safe,” said Kendra Klein, deputy director for science at Friends of the Earth and an author of a 2020 report that calls gene-silencing pesticides “a vast, open-air genetic experiment”. “We are considering releasing a material into the environment that will genetically engineer organisms in real time. We have such a long history of unintended consequences of technologies in agriculture – it would be foolish to not assume that there will be unintended consequences to this technology.”

The gene-silencing mechanism used by such pesticides can be triggered whenever they encounter a matching or similar genetic sequence, noted Klein.

“We’re talking about potentially thousands of other species that would have related genetic sequences,” she said. 

The EPA said in a press release that EUP experimental testing will continue during the initial commercial registration period and data from it “may be used in a future application for this product to amend its directions for use.”

But critics said that is not sufficient. The EPA should know, for instance, how spraying the pesticide might affect species other than the intended target, including endangered beetles and the birds and amphibians that prey on the potato pest, said Jaydee Hanson, the policy director at the Center for Food Safety.

“The EPA had done a pretty good job leading up to their abrupt notice that they wanted to approve this as a pesticide,” said Hanson. “It’s not a bad job for the start of a field trial. But it’s a grossly incomplete job for turning this into an approval of the pesticide.”

Immune response and efficacy concerns

Consumer Reports’ Hansen said he commends the EPA for having the company consider effects on endangered species and for looking at both the active ingredient and the formulated product when conducting tests. “Those are big steps forward,” he said. 

However, Hansen remains concerned about the possibility that the new pesticide could trigger an immune system response in humans. An analysis by GreenLight Biosciences previously identified two human transcripts that could potentially be affected by ledprona, although the final EPA human health risk assessment states that “there is a reasonable expectation that ledprona is unlikely to affect these genes in vivo.”

“But they don’t present enough data for us to see whether that’s true,” said Hansen.

The EPA notes in the assessment that double-stranded RNA molecules that are on the longer side, such as ledprona, “are generally considered candidates to induce innate immune responses.” As a result, the agency concludes that farmers and others working with the pesticide should wear respirators to avoid any risks from inhaling the pesticide. 

However, the agency is not requiring “any kind of verification that everyone’s going to be wearing [personal protective equipment] or even monitoring any of those folks to see if anything is happening,” Hansen said. “It seems to me almost like a ‘don’t look, don’t find’ strategy.”

Hansen also wonders about the pesticide’s efficacy – and the efficacy of RNAi pesticides more generally. A 2021 Scientific Reports study assessed a similar double-stranded RNA, which was being developed for a spray to combat the same potato pest. It found that within nine generations, 11,100 times the original quantity of pesticide was needed to get the same effect – an “extremely high” level of resistance, according to the study itself. 

“I would want to see the same thing on this product [ledprona] before it was ever approved, because if it does select for resistance very rapidly, that’s not useful,” said Hansen. “With most chemical pesticides you don’t see something like that,” he added. “That caused me to wonder if this whole field will just collapse.”

(Featured image: Colorado potato beetle. Photo by Олександр К on Unsplash.)