ABOVE: Aphids feed on a corn plant.

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An ongoing basic research program from the US Defense Advanced Research Projects Agency called Insect Allies faces criticism in an op-ed published today (October 4) in Science. The commentary’s authors express concerns about the development and possible dispersal of insect vectors to deliver genetically modified viruses to crops. Namely, they say the technology could be seized for the development of biological weapons.

“Although we are not ourselves accusing DARPA of weaponizing the program, our main concern with this is that it could give the appearance of weaponization to other countries who may themselves want to establish their own programs like this,” coauthor Derek Caetano-Anollés, a postdoc at the Max Planck Institute for Evolutionary Biology, tells The Scientist.

Insect Allies participants and supporters contend that the research has appropriate precautions in place and that it could lead to solutions to the growing challenges facing agricultural production.

“We’re doing fundamental research [with] viruses and insect vectors to see if we can use them to confer positive traits to plants that in the future could be used to help protect . . . important US crops,” says Bryce Falk, a plant biologist at University of California, Davis, who receives funding from the Insect Allies program. All of his team’s research takes place within a Biosafety Level 3 facility, so nothing is released into the environment.

The Defense Advanced Research Projects Agency (DARPA) is an arm of the Department of Defense that funds research projects to develop new technology for defensive uses. Its Insect Allies program solicited proposals from researchers in late 2016, with the intention of funding projects that would use insects to deliver viruses carrying specific traits to modify crops during one growing season. For instance, researchers could engineer a plant virus to deliver modified genes to adult maize plants that would help them cope with drought or disease. They would use insect vectors to deliver the virus, leading to expression of the chosen protective genes in the adult plants during a single growing season.

There are really legitimate reasons that you would want to promote crops with certain capabilities and . . . there are legitimate concerns to be raised. —Daniel Gerstein, RAND Corporation

In 2017, DARPA awarded four years of funding, a total of about $30 million, to four research teams in the US.

The authors of the critique say this is the first program to fund the development of viruses specifically designed for possible release into the environment to edit the genomes of target species, possibly with CRISPR-based strategies. Their concern is that the application could affect the seeds of plants and disrupt future growing seasons.

More generally, the critics also suggest that releasing genetically modified viruses could potentially infect organisms beyond those they’re aimed at. “If we choose to use this technology, this is something that you could see arising again and again and again, not just in agriculture,” says coauthor R. Guy Reeves, a postdoc at the Max Planck Institute for Evolutionary Biology.

Entomologist Blake Bextine, DARPA program manager for Insect Allies, says transgenerational genetic modifications are not in the works. “All of our teams are actually working with transient expression systems,” meaning that the introduced genetic material does not alter chromosomes or the germ line, and thus would not affect future plant generations.

“It’s a very useful idea to use transient expression,” says Vitaly Citovsky, a plant biologist at Stony Brook University in New York who is not affiliated with the Insect Allies program. “Most plant viruses are not seed-transmissible, which means if a plant is infected by the virus, no matter what the virus does, even if [it] genetically modifies plants stably using CRISPR-Cas9, the virus does not get to the seeds.”

Caetano-Anollés, Reeves, and colleagues also express concern about the lack of discussion in official Insect Allies materials on the regulation of both the viral technology and the recipient crops. They highlight the extra layer of complication added by using insects, which would have to be raised near the target farms and have some kind of kill switch built in to ensure that they don’t reproduce, and propose spraying viruses as a simpler, alternative application system.

Falk explains that just spraying a virus on likely wouldn’t allow it to infect the plant. “To enter plants, viruses have to get through the tough cell wall,” he says. “The wounding of the plant cell is in the vast majority of cases achieved by the vector entering the plant cell to feed, and in [most] cases this is by insect vectors—typically aphids, whiteflies, or leafhoppers.”

Additionally, the authors discuss the Biological Weapons Convention, which prevents the development and stockpiling of biological weapons and was ratified by 22 countries of the United Nations in 1975. They write that a 2012 update to this agreement might apply to the intent of the Insect Allies program, as it uses insects to infect plants with genetically modified viruses. Caetano-Anollés, Reeves, and colleagues explain that the technology in the Insect Allies program could be harnessed as a weapon to, say, disrupt crop production, by simply removing the safeguards DARPA requires—for instance, that insect vectors die within a few weeks of their release.

In answer to questions about regulating the developing technology, Bextine points to the ongoing involvement in the project of representatives from regulatory agencies, such as the US Department of Agriculture, the Food and Drug Administration, and the Environmental Protection Agency. He adds that the project specifically has a nongovernment team in place to help DARPA address the ethical, legal, and social implications of the program, which, he says, is specifically in line with guidelines from the Biological Weapons Convention.

Despite the differing viewpoints, both sides are willing to engage in discussion about the Insect Allies program. “The intent of the piece . . . is that we want this to have more attention,” says Caetano-Anollés.

Academic research is “supposed to bring up questions and have these types of conversations,” says Bextine. “I’m comfortable doing that, and I’m glad that we have the opportunity to have the conversation first and foremost.”

“These types of dialogues are extremely productive,” says Daniel M. Gerstein, a biosecurity policy researcher for the RAND Corporation. “There are really legitimate reasons that you would want to promote crops with certain capabilities and . . . there are legitimate concerns to be raised.”

R.G. Reeves et al., “Agricultural research, or a new bioweapon system?” Science, doi:10.1126/science.aat7664, 2018.