Annotated-DARPA Oct 5th response

Below is the full text of the response  posted by the DARPA on the Insect Allies web page. Response to Science Opinion Piece - Oct 4 2018.pdf

We would note the absence of clear statements on the following 

  • No text identifying factual inaccuracies in Science article
  • No statement suggesting that  gene editing of plant chromosomes by viruses was never a goal of the Insect Allies program, as has recently been suggested.
  • No text stating that gene editing of plant chromosomes, including plant gene disruption,  by GM viruses is specifically prohibited for all 3 consortia (the significance of  to transfer modified, protective genes to plant” below  is ambiguous). See  also page  Is gene editing of plant chromosomes even part of the Insect Allies program?
  • No text stating that accidental or intentional editing of seeds is  prohibited for all consortiaSee also page
  • No explanation or publication of documents explaining how farmers, seed producers or consumers who might not want to participate in the use of this technology could opt-out—a right under the long-term policies of the USDA and many other countries—.
  • Lots of agricultural research (commercial and USDA funded) seeks to address many of the same food security concerns mentioned in the DARPA response, however there is no explanation or publication of documents explaining in detail why these programs are  likely to prove so  inadequate as to justify proposing such a  “technologically high-risk project”.

  • No text explaining how early proliferation of the information necessary for biological weapons development will not occur prior to any system that might conceivably be controllable enough for routine agricultural use.  This includes the potentially imminent concern raised in the Science article “[publication] of what may be seen as preliminary instruction manuals on how to develop offensive HEGAA programs, directed in the first instance against maize.
  • We are obviously not advocating in our article for spraying and any discussion on the relative merits of spraying technologies and who should develop it is a distraction.

Text of the DARPA statement below has been highlighted by based on its predominant topic in the following colours.

Text largely aimed at asserting that expert discussions had occurred about the Insect Allies program.

Our article refers only to public discussion ( x8 times). Private discussions, however expert, cannot substitute for broad informed public debate.

We would observe, were a low bar of substantially private discussion established as a norm, then it will also likely be applied by any other state, company or foundation funding similarly risky directions of GM virus  research.

Text clearly  stating  new technical information on how the stated aims of the Insect Allies program are being realised.

Providing this information, that only DARPA has access to, is key to having an informed public debate— its absence can only foster speculation on topics of obvious concern—.

Text relating to discussing spraying 

We are obviously not advocating in our article for spraying and any discussion on the relative merits of spraying technologies and who should develop it is a distraction.

 However, in the brown text there does appear to be an acknowledgment  that spraying is indeed more controllable, though a new argument is advance  here  “DARPA would never fund the next generation of aerial spraying technology; that is the role of industry and other research funders”. That proven and more controlled approaches exist but are not sufficiently avant-garde for the funder, might also be seen as an argument against the appropriateness of DARPA directing agricultural research. 

In comments to  Abby Olena of the The Scientist  the following logical argument was  presented “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.”

Though this may benefit from discussion in the context of   field trials in Kentucky [1]  where viruses were successfully sprayed on to tobacco plants to infect .

[1] “Virions were mixed with an abrasive and spray inoculated on either greenhouse-grown or field-grown plants” see review in Pogue, G. P.; Vojdani, F.; Palmer, K. E.; Hiatt, E.; Hume, S.; Phelps, J.; Long, L.; Bohorova, N.; Kim, D.; Pauly, M.; Velasco, J.; Whaley, K.; Zeitlin, L.; Garger, S. J.; White, E.; Bai, Y.; Haydon, H.; Bratcher, B. Production of pharmaceutical-grade recombinant aprotinin and a monoclonal antibody product using plant-based transient expression systems. Plant Biotechnology Journal 2010, 8, 638–654, doi:10.1111/j.1467-7652.2009.00495.x.

Statement from Dr. Blake Bextine, DARPA Program Manager for Insect Allies

As the DARPA program manager for Insect Allies, I appreciate the thought that went into the critique of the program presented in Science, though I disagree with its conclusions. Technologies dealing with food security and gene editing certainly do have a higher bar than most for transparency, research ethics, and regulatory engagement, and I believe Insect Allies meets that raised standard. DARPA structured Insect Allies as a university-led, fundamental research program, and has invited in representatives from U.S. regulatory agencies from the very beginning of the program to offer perspectives and learn about the work. The researchers working with DARPA are free and encouraged to discuss their efforts, publish results, and coordinate with regulatory agencies to facilitate the transition of their technologies from laboratory demonstrations to—someday in the future—powerful new tools that can bolster the toolkit for responding to fast-moving or unanticipated threats to the global food supply.

DARPA created Insect Allies to provide new capabilities to protect the United States, specifically the ability to respond rapidly to threats to the food supply. A wide range of threats may jeopardize food security, including intentional attack by an adversary, natural pathogens, and pests, as well as by environmental phenomena such as drought and flooding. Insect Allies aims to develop scalable, readily deployable, and generalizable countermeasures against potential natural and engineered threats to mature crops. The program is devising technologies to engineer and deliver these targeted therapies on relevant timescales—that is, within a single growing season. To do so, Insect Allies researchers are building on natural, efficient, and highly specific plant virus and insect vector delivery systems to transfer modified, protective genes to plants. Since the start of the program, Insect Allies teams with expertise in molecular and synthetic biology have demonstrated mounting technical breakthroughs that are providing foundational knowledge in plant virus gene editing and disease vector biology from which the program will continue to build.

Spraying of HEGAAs versus insect means of viral delivery

Our inclusion of a short section  of text about spraying  was clearly not to advocate for the spraying of HEGAAs, it was to highlight the implausibility of the sole motivation so far presented by DARPA for mandating insect dispersion. See more details on FAQ page, including link to established technology successfully spraying plant viruses in fields experiments. 

We note that while  DARPA restated the same  efficiency argument considered in the article,  it does advance  a new one here  “DARPA would never fund the next generation of aerial spraying technology; that is the role of industry and other research funders”. That more controlled approaches might exist but are not sufficiently avant-guarde for the funder, might also be seen as an argument against the appropriateness of DARPA directing agricultural research.

State-of-the-art methods and technologies for protecting staple crops, and especially mature plants, are not up the challenge of responding quickly and at scale to the most severe threats. The authors of the Science piece point to spraying technologies as an effective solution, but their argument overlooks some of the key elements that Insect Allies aims to address. Namely, many existing methods for protecting crops are inefficient, expensive, imprecise, or destructive to plants, may require significant infrastructure, and often provide only limited efficacy. Sprayed treatments are impractical for introducing genetic modifications on a large scale and potentially infeasible if the spraying technology does not access the necessary tissues with specificity. Meanwhile, traditional selective breeding methods for introducing protective traits into plants require years to propagate, nowhere near the speed required to prevent a fast-moving threat from developing into a crisis.

DARPA made the move into agriculture for two reasons. First, the stability of our domestic agricultural sector represents a critical, but often under-appreciated element of national security. If DARPA can deliver technologies that keep the U.S. resilient in the face of threats, we preserve stability and readiness at home and diminish a source of instability abroad. Second, DARPA has a unique charter to pursue revolutionary and technologically high-risk projects that go well beyond the incremental advances typical of many other research and development organizations. DARPA would never fund the next generation of aerial spraying technology; that is the role of industry and other research funders. Instead, we reach for fundamentally new ways of delivering more precise, efficacious treatments through systems that can be readily adapted to confront a range of potential threats.

Part of the DARPA model is to demonstrate proof of concept and remove degrees of risk from a new technology to facilitate its eventual transition to an end user. For Insect Allies, we scheduled a four-year program of research that concludes with demonstrations inside large, biosecure greenhouses. At no point in the program is DARPA funding open release of Insect Allies systems. Regulatory approval has been a part of the program since its inception as it would be necessary for any eventual realization of the technology. Interactions with regulators have provided comprehensive and alternative perspectives to the DARPA-funded efforts, and updates from our researchers help to inform the evolution of new guidelines and policies by those very same regulators. Representatives from the U.S. Food and Drug Administration, Environmental Protection Agency, and Department of Agriculture’s Animal and Plant Health Inspection Service (Biotechnology Regulatory Services and Plant Health) and Agricultural Research Service participate in Insect Allies meetings and program reviews. One illustration of this dynamic between DARPA, researcher, and regulator is the criticality of building in safeguards and limitations to Insect Allies technology. Every performer in the program is required to include at least three independent kill switches in their systems to shut down functionality of the technology. This is in addition to bio-containment requirements in the active program.

The stakeholder interactions mentioned above are ongoing, and I offer a few examples of participants and their contributions:

Evidence of public debates

We attempted to locate any public information on the  content of the 4  presentations mentioned,  by internet searchers and kind and thoughtful responses to inquiries we can provide the following links.

Dr. Jacqueline Fletcher (see last 10 slides)

Dr. Richard Murray (probably similar to the slides in this NAS report)

Dr. Sonny Ramaswamy (did not recall using slides)

  • Dr. Jacqueline Fletcher of the National Institute for Microbial Forensics & Food and Agricultural Biosecurity at Oklahoma State University and Dr. Sonny Ramaswamy, then director of USDA’s National Institute of Food and Agriculture, both spoke at the Insect Allies Proposers Day on November 18, 2016.
  • Dr. Richard Murray, Thomas E. and Doris Everhart Professor of Control & Dynamical Systems and Bioengineering at the California Institute of Technology, presented on a National Academies report titled “Preparing for Future Products of Biotechnology” at the Insect Allies kickoff meeting on August 14, 2017.
  • Georg Jander, principal investigator for the Insect Allies team led by The Boyce Thompson Institute, presented results and perspective to the Trilateral Technical Working Group (TTWG) on May 31, 2018. The TTWG is composed of agricultural biotechnology regulators from the United States, Canada, and Mexico.
  • The Insect Allies program benefits from the input of independent advisors on legal, ethical, environmental, dual-use, and responsible innovation (LEEDR) topics. These advisors include: Dr. Richard Murray (Caltech); Dr. Jim Stack, Fellow, Biosecurity Research Institute/Professor, Department of Plant Pathology/Director, Great Plains Diagnostic Network, Kansas State University; and Dr. Paul Thompson, W. K. Kellogg Chair in Agricultural Food and Community Ethic, Michigan State University.

Emerging biotechnologies—and especially the cutting-edge research being performed on Insect Allies— are pushing science into new territories. DARPA is proud to be taking a proactive role in working with stakeholders to inform a new framework for considering how the benefits of these technologies can be most safely realized. 

The  DARPA response was posted on the DARPA website on the 4th of October, but it had been prepared several days earlier using an embargoed copy of the Science article first released on September the 30th.

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