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).
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]
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.
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.
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]