Horizontal Environmental Genetic Alteration Agents Explained

Horizontal Environmental Genetic Alteration Agents (HEGAAs) are any artificially developed agents that are engineered to edit the genome of eukaryotic species they infect when intentionally dispersed into the environment (outside of contained facilities such as laboratories or hospitals).

History

The term “genetic alteration agent” first appears in a 2016 work plan by the Defense Advanced Research Projects Agency (DARPA) describing a tender for contracts to develop genetically modified plant viruses for an approach involving their dispersion into the environment.[1] The prefixing of “horizontal environmental” to the former to generate the acronym HEGAA was first used in a 2018 scientific publication.[2] The acronym HEGAA or its plural HEGAAs has subsequently been used in scientific [3] [4] defence[5] and general media.[6] [7]

General usage

Agents such as pathogens, symbionts or synthetic protein assemblages [8] that can be acquired through horizontal transmission in the environment can potentially be engineered to become HEGAAs. This would be achieved using biotechnology methods to confer to them the capacity to alter nucleotides in the chromosomes of infected individuals through sequence-specific editing systems like CRISPR, ZFNs or TALENs. No known infectious agent naturally has the capacity to gene edit eukaryotes in a manner that can be flexibly targeted to specific sequences (distinct from substantially random natural processes like retroviral integration).

By definition, HEGAA induced gene editing events are intended to occur outside of contained facilities such as laboratories or hospitals. While genetically modified viruses with CRISPR editing have been successfully used as research tools in laboratories [9] [10] or for gene therapy in clinical settings, all gene editing events are intended to physically occur within contained facilities. By contrast, HEGAAs for their intended mode of action relies on inducing gene editing events that occur largely or exclusively in the environment.

Where HEGAAs are engineered to target obligate sexually reproducing species they can usefully be thought of being of two types:-

Where HEGAAs are engineered to target host species that can reproduce asexually, for example vegetatively reproducing plants, the above distinctions are largely no longer meaningful.

Despite an expanding number of techniques which employ engineered infectious agents to alter the genetic material of a second species, often involving genetically modified viruses, only a very small minority rely on gene editing events occurring in the environment. Furthermore, while there are a number of proposed applications which rely on the intentional dispersion of genetically modified infectious agents in the environment, only those where gene editing occurs are considered HEGAAs. Consequently, proposed applications of viral immuno-contraception,[11] [12] transmissible vaccines,[13] [14] and agricultural field transient expression systems [15] [16] are not examples of HEGAA approaches, because none currently involve gene editing. HEGAAs are only those agents that are proposed for applications that require both horizontal acquisition (infection) and gene editing events that are intended to occur in the environment.

No HEGAAs have been intentionally dispersed into the environment, though some are reportedly in development.

HEGAAs in development

Insect Allies program

Horizontal Environmental Genetic Alteration Agents is agricultural technology currently being developed by DARPA to ensure long term food security. It is under research in DARPA known as the Insect Allies project.[17] On a high level, insects serve as vectors to "infect" crops with a virus to alter their genes to become more resilient against pests, weeds and climate changes.

HEGAA like scenarios in fiction

Fictional plagues of engineered pathogens have been a feature of science fiction literature considerably prior to the advent of targetable gene editing systems. However, despite informed conjecture in media sources [18] [19] [20] or reports [21] on HEGAA like scenarios, there have been few in a fictional context.

An example of a HEGAA like scenario is a storyline in the season 10 of The X-files, with a virus engineered to contain a CRISPR system targeted to disrupt the sequence of the human adenosine deaminase gene. Gene editing of the virus is triggered in the environment as a means to destroy the human immune system in the fictional story.[22]

Notes and References

  1. Web site: Broad Agency Announcement Insect Allies, Biological Technologies Office, HR001117S0002 November 1, 2016 .
  2. Reeves RG, Voeneky S, Caetano-Anollés D, Beck F, Boëte C . Agricultural research, or a new bioweapon system? . Science . 362 . 6410 . 35–37 . October 2018 . 30287653 . 10.1126/science.aat7664 . 2018Sci...362...35R . 21.11116/0000-0002-4F53-9 . 52921548 . free .
  3. Simon S, Otto M, Engelhard M . Scan the horizon for unprecedented risks . Science . 362 . 6418 . 1007–1008 . November 2018 . 30498119 . 10.1126/science.aav7568 . Jennifer . 2018Sci...362.1007S . 54168410 . Sills .
  4. Web site: Pentagon's pursuit of insect-delivered genetic modification of crops prompts warnings. October 2018. Rebecca . Trager. vanc . Chemistry World. en. 2019-06-10.
  5. Web site: Scientists: Pentagon's Plant-Virus Research Could Endanger World's Food Supply. Defense One. 2019-06-10.
  6. Web site: DARPA is making insects that can deliver biological weapons, scientists have claimed . Hannah . Osborne . vanc . 2018-10-04. Newsweek. en. 2019-06-10.
  7. Web site: Could We Turn Insects into Biological Weapons?. 2018-10-17. American Council on Science and Health. en. 2019-06-10.
  8. Butterfield GL, Lajoie MJ, Gustafson HH, Sellers DL, Nattermann U, Ellis D, Bale JB, Ke S, Lenz GH, Yehdego A, Ravichandran R, Pun SH, King NP, Baker D . 6 . Evolution of a designed protein assembly encapsulating its own RNA genome . Nature . 552 . 7685 . 415–420 . December 2017 . 29236688 . 10.1038/nature25157 . 2017Natur.552..415B . 5927965 .
  9. Ali Z, Abul-faraj A, Li L, Ghosh N, Piatek M, Mahjoub A, Aouida M, Piatek A, Baltes NJ, Voytas DF, Dinesh-Kumar S, Mahfouz MM . 6 . Efficient Virus-Mediated Genome Editing in Plants Using the CRISPR/Cas9 System . Molecular Plant . 8 . 8 . 1288–91 . August 2015 . 25749112 . 10.1016/j.molp.2015.02.011 . free .
  10. Ran FA, Cong L, Yan WX, Scott DA, Gootenberg JS, Kriz AJ, Zetsche B, Shalem O, Wu X, Makarova KS, Koonin EV, Sharp PA, Zhang F . 6 . In vivo genome editing using Staphylococcus aureus Cas9 . Nature . 520 . 7546 . 186–91 . April 2015 . 25830891 . 4393360 . 10.1038/nature14299 . 2015Natur.520..186R .
  11. Torres JM, Sánchez C, Ramírez MA, Morales M, Bárcena J, Ferrer J, Espuña E, Pagès-Manté A, Sánchez-Vizcaíno JM . 6 . First field trial of a transmissible recombinant vaccine against myxomatosis and rabbit hemorrhagic disease . Vaccine . 19 . 31 . 4536–43 . August 2001 . 11483281 . 10.1016/S0264-410X(01)00184-0 . 20.500.12792/4539 . free .
  12. Web site: Virus could sterilise Australia's rabbits. O'Neill. Graeme. vanc . 2002. www.newscientist.com. 2019-06-10.
  13. Bull JJ, Smithson MW, Nuismer SL . Transmissible Viral Vaccines . Trends in Microbiology . 26 . 1 . 6–15 . January 2018 . 29033339 . 10.1016/j.tim.2017.09.007 . 5777272 .
  14. Nuismer SL, Althouse BM, May R, Bull JJ, Stromberg SP, Antia R . Eradicating infectious disease using weakly transmissible vaccines . Proceedings. Biological Sciences . 283 . 1841 . 20161903 . October 2016 . 27798311 . 10.1098/rspb.2016.1903 . 5095390 .
  15. Pogue GP, Vojdani F, Palmer KE, Hiatt E, Hume S, Phelps J, Long L, Bohorova N, Kim D, Pauly M, Velasco J, Whaley K, Zeitlin L, Garger SJ, White E, Bai Y, Haydon H, Bratcher B . 6 . Production of pharmaceutical-grade recombinant aprotinin and a monoclonal antibody product using plant-based transient expression systems . Plant Biotechnology Journal . 8 . 5 . 638–54 . June 2010 . 20514694 . 10.1111/j.1467-7652.2009.00495.x .
  16. Web site: Southern Gardens Citrus Nursery, LLC; Notice of Intent to Prepare an Environmental Impact Statement for Permit for Release of Genetically Engineered Citrus tristeza virus . www.regulations.gov. 2019-06-10.
  17. Web site: DARPA Enlists Insects to Protect Agricultural Food Supply and Commodity Crops. www.darpa.mil.
  18. Web site: Can There Be War Without Soldiers?. Brooks. Rosa . vanc . Foreign Policy. en-US. 2019-06-10.
  19. Web site: Top U.S. Intelligence Official Calls Gene Editing a WMD Threat. Regalado. Antonio. vanc . MIT Technology Review. en-US. 2019-06-10.
  20. Book: Block, Steven. Living nightmares: Biological warfare threats enabled by molecular biology. In The New Terror: Facing the Threat of Biological and Chemical Weapon. vanc. Hoover Institution Press. 1999. 978-0817997014. registration.
  21. Hauck. Daryl J.. vanc . 2005. Pandora's Box Opened Wide: UAVs Carrying Genetic Weapons. https://web.archive.org/web/20220601070213/https://apps.dtic.mil/docs/citations/ADA463462. live. June 1, 2022. RAND Corp.. en.
  22. Web site: CRISPR patent belongs to aliens : A view From the Bridge. blogs.nature.com. 2019-06-10.

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