PATHOGEN LIBRARY

 
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Chronicling the emergence of Genetically Modified Organisms and other unintentionally ‘altered’ genomes across our biome – documenting synthetic changes to the living genetic code by biotechnologies, as part of an observatory for the long-term monitoring of unpredictable pathways for future life.

 

ABOUT 'PATHOGEN LIBRARY'

 

“We can, if we wish, reduce this threat to our genetic heritage, a possession that has come down to us through some two billion years of evolution and selection of living protoplasms, a possession that is ours for the moment only, until we must pass it on to generations to come. We are doing little now to preserve its integrity.”

 

This sentiment, penned by the late biologist and conservationist Rachel Carson in Silent Spring, poignantly refers to the incremental damages accruing in genomes as a result of humanities’ casual use of, and exposure to, hazardous bio-chemical substances, alongside sources of ionising radiation. Such latent injuries to DNA are accumulative, manifesting indiscriminate damage across the genetic material of an exposed organism over the entirety of its lifespan, which may thereafter impact it’s own long-term vitality, lifestyle, and health, alongside that of it’s wider exposed species and biome. However, the long-term impacts of this damage to an organism's inherited germline, bequeathed to subsequent offspring and distant posterity of the afflicted species, is less-frequently investigated despite the proliferate use of these synthetic substances. Much of these incurred changes to the genetic code are random and sporadic, presenting an incalculable number of mutations – beneficial or (likely) adverse – which may or may not filter down throughout the ages to descendant organisms by means of well-studied Vertical Gene Transfer (VGT) reproduction channels. As Carson surmises, this Anthropogenic modification of life’s genetic material through environmental exposure to toxic synthetic substances creates radical changes to genomes that might not even be beneficial today, in comparison to ‘natural’ background evolutionary processes, which occur over protracted timescales.


Since Carson’s salient warning over sixty years ago, synthetically induced changes to the genetic code from unintentional Anthropogenic processes can be readily observed across many kingdoms of life through present [limited] studies of environmental pollution on complex ecosystems. For instance in human populations, birth defects from inherited genetic damage are still readily apparent across dioxin-sprayed regions of Vietnam and other regions of South-east Asia during the Vietnam War. Studies of other POPs and compounds of concern, like Hexavalent chromium (Chromium-6), have also illustrated the profound damage these hazardous substances can impart on an organism’s inheritable genome, in addition to well-documented monitoring programs for the offspring of populations still living out their lives in radiologically-contaminated landscapes. Never before has humanities’ enchantment with it’s own technological proficiency possessed the capability to intentionally (or negligently) harm the genetic inheritance for all future generations in many unpredictable ways, but we are still under one century removed from the proliferation of these now-recognised hazardous technological ventures and unregulated substances – precarious legacies which continue to have long-term environmental, material, generational, and genetic implications.


In stark contrast to these unintentional and negligent channels that profoundly modify the genetic code inherited by successive generations, in the late 21st century our species has ushered in the dawn of another facet of our ‘advancing’ age through purposeful genetic engineering technologies; placing the power to radically (and rapidly) alter the future germlines of many species exclusively in the hands of a few contemporary homo sapiens. Our species, in effect, becomes a “self-appointed priesthood” for this new transformative technological era, further enabling us to enact vast biological changes in accordance with the ambitions of our other material culture domains. Perhaps, the most well-known genetic engineering technique is CRISPR gene editing; a family of DNA sequences and an enzyme (Cas9) that enable a geneticist to accurately ‘cut and paste’ targeted segments of an organism's genetic code, in accordance with the desires of the genetic engineer. By delivering the Cas9 nuclease coupled with a synthetic guide RNA (gRNA) into a cell, the genome can be simply cut at a desired location, allowing existing genes to be entirely removed, while also enabling the insertion of newer genes at desired locations in vivo (in living organisms). After this synthetic modification to the cells genes, this inheritable ‘edit’ is then expressed across all successive cells in the genetic lineage through the known processes of cell division, and subsequent VGT ‘sex’ channels. Notwithstanding the ‘vandalism of the genomes of Earth’ arguments, many proponents of genetic engineering have illustrated the crucial benefits for this biotechnology. Indeed, there are immediate benefits. As an example, the germline for staple crops (such as the water-intensive strains of corn) can now be modified to prosper in harsher arid climates by inserting a foreign gene that reduces crop dependencies on water, thus economising the agricultural sector by increasing farming yields. Other gene modifications could enable a crop to produce pesticides in vivo – reducing losses to predation.


Certainly, there are very human advantages for the synthetic modification of genomes in targeted organisms. At present, genetic engineering is touted to advance modern human societies across a plethora of medical, industrial, agricultural, epidemiological, and ecological sectors. In spite of these frequently acclaimed advantages though, these recent technologies may also unintentionally produce “revenge effects” in the environment we have yet to observe or encounter; ‘revenge effects’, defined by Edward Teller, as inadvertent consequences resulting from an indiscriminate adoption of newer technologies, without broader scrutiny, foresight, or considerations for the unintended side effects that can “bite back”. An early, germane example for the technical, democratic, and ethical facets of this technological complexity that can already be observed in the discovery of unapproved genetically-modified wheat amongst unaltered wheat species strains on an Oregon farm – much to the ire of the non-GMO farmer. The intent here is not to engage with debates surrounding the safety of GMO food consumption, but rather to illustrate the inadvertent spread of purposefully modified genetic materials outside of direct human supervision which highlights much of the contention, and enduring concerns, associated with this technologies’ widespread adoption. Perhaps, the dynamics of this debate also demonstrates early signs for yet another wayward technological legacy that will subsequently manifest problems for distant posterity – generations who cannot readily have a say over our choices or edits to the integrity of Earth’s inheritable genomes. Surely – and in retrospect – this short-termism thinking demonstrated in the past proliferate use of ‘advanced technologies’, such as pesticides and other ‘wondrous’ substances now identified as POPs, should pre-empt our species to err on the side of precaution until adequate investigations on the causal effects of genetic engineering within a living biome can be concluded. This would require multigenerational vigilance, observation, technical studies and, perhaps more crucially, foresight to fund this scientific scrutiny.


The emergent frontier of ‘genetic interventionism’ raises an abundance of fundamental ethical complexities, and profound philosophical questions in relation to humanity's stewardship activities (especially the moral implications for preserving the integrity of the human germline, discussed extensively in GM literature). But, as established above, it also casts a protracted shadow across our biome. The CRISPR-Cas9 technique enables geneticists to specifically cut a cell’s genome in a specific location, while introducing newer genetic material into this region that nature never intended. These genetic modifications are finely targeted – enabling the geneticist to insert a desired gene, to express a desired trait, in a desired genetically modified organism, for the purposes of synthesising an intended product or desired outcome. However, the durational stability of these ‘rough edits’ made with this nascent technology are unknown – specifically, will these edits remain viable for fulfilling this stated intent over a period of deep time in nature? DNA for any organism is, after all, a dense, genetic library which documents billions of years of irreducible computation in phylogenetic evolution, redundant mutations, genetic mistakes, and biological adaptations to specific ecosystems, alongside serving as a hereditary blueprint for all ancestral organisms. The ‘original’ unaltered sequences of DNA are ‘tried and tested’ over eons due to the uncompromising focus of evolution, ensuring that the genetic code for species and their descendants remains (primarily) stable from widespread transcription errors, while also catering for subtle changes to manifest advantageous mutations (otherwise, the maladapted organisms often die out over time – but not always). However, ‘rough edits’ synthesised through genetic engineering techniques possess much less certainty, given the lacunae in our knowledgebase for observing these expressed traits in nature over required timescales (we have none). Long-term experiments and observation programs (preferably in laboratory settings) may one day elucidate some answers over multiple centuries, however designing such studies is a difficult affair, fraught with scientific uncertainty at all stages. Experiments certainly shouldn't be conducted in open ecosystems, with variables far beyond the experimenter's controls.


Coupled with this open question of longevity for GMOs through VGT channels (i.e., successive offspring inheriting genes), the natural circumstances that enable Horizontal Gene Transfers (HGT) between species should also provoke cause for protracted concern. Known otherwise as lateral gene transference, this vector differs from the traditional ‘linear’ processes of VGT movements for genetic inheritance insofar as genes are transferred via displaced genetic fragments between species rather than through successive natural evolutionary pathways – essentially leading to the expression of advantageous genetic traits in unrelated organisms that are capable of adopting foreign genetic materials. This type of transfer network for genetic material is frequently observed in prokaryotes; bacteria who readily uptake foreign genes into their plasmids via bacteriophages and other transfer mechanisms, before expressing these rouge genes for their own ecological advantage (for example, rapidly developing methods of resistance to certain antibiotics). This recombinant DNA pathway was exploited in Cold War biological warfare programs to create new strains of mutant pathogens which were resistant to known medical treatments, far more virulent than natural variants, and much more contagious. The USSR Biopreparat program is of particular note. However, recent observations have concluded that prokaryotes across all kingdoms of life also avail of HGT to some limited extent – the term ‘limited’ here acknowledging the extent of our understanding for the role of HGT in the natural genetic world, as opposed to denoting any boundary on the capabilities of HGT in prokaryotic life.

Tardigrades have been observed to be serial beneficiaries from HGT networks, some even acquiring about one-sixth of their total inheritable genetic material from unrelated organisms. However, larger multicellular organisms have also been scientifically inferred to benefit from these lateral transfers of genetic material. For instance, both herring and smelts (both cold-dwelling fish species) produce anti-freezing proteins in their blood to prevent crystallisation, however both species produce this substance in the exact same way – despite the species having diverged over 250 million years ago, and the gene being absent from all other related fish species along their phylogenetic lineages. Hybridisation or established ‘sex channels’ between species isn’t genetically possible, pointing to lateral inheritance of genes as the likely route of genetic acquisition – leading us to question how often this process of genetic material exchange occurs across species barriers, and between disparate branches on the tree of life. Some studies have raised this exact question. For instance, grass species have been continually observed to exchange genetic materials between lineages that have evolved significant reproductive barriers; enabling the colonisation of new ecological niches by creating novel phenotypes. As the evolutionary genomicist Sarah Schaack poignantly stated of such transfers; “How often am I actually taking up a piece of DNA from my environment, and I don’t know it?” Genetic inheritance is, apparently, not as straightforward as neatly defined in mainstream biology textbooks.

In regards to the assumed reliability of genetic engineering technologies to ensure desirable traits manifest in a desirable target species only, these recent observations of ‘natural’ genes transmission within the HGT avenue raises concern for how stable and isolated our rough edits will remain within intended genetically modified populations, in the face of living ecological systems, and also over protracted intervals of deep time. How might GMOs, some designed to essentially outcompete and outproduce unaltered strains of the same species, someday transfer these advantageous traits to the unaltered germlines of unrelated species? Certainly, some species of unfavourable flora presently classified as ‘weeds’, if they can inherit advantageous genes from nearby GMO crops residing in the same harsher climates, would wholly benefit if HGT processes can transfer useful genetic material; producing a proliferation species of ‘Unintentional-Genetically Modified’ (U-GM) weeds, which are equipped to outcompete surrounding plant life and human control measures. Adaptations to the latter Anthropogenic measures has precedence in the very recent past; as seen in weeds developing an immunity to herbicides, in addition to mosquitos rapidly developing resistance to DDT and other insecticides. Such genetically-induced advantages may also inevitably impact entire ecological webs and species populations – for instance, assimilating foreign genes that synthesise natural insecticides would greatly reduce predation niches; blindly creating a feedback that may lead to a keystone species’ population decline or total extinction. It is easy to speculate how such profound knock-on effects may lead to undesirable outcomes, especially when given enough time to evolve.

As documented elsewhere in the After the Horizon research program, the control of human pathogen vectors is not a new socio-technological endeavour. However, the adoption of genetic engineering techniques in pest elimination campaigns, such as the Alexander Serebrovsky/ Edward Knipling method known as the Sterile Insect Technique (SIT), introduces yet another technological facet to achieve this biological control campaign. The conception of ‘Gene Drives’ for the SIT method – a process by which a deleted, faulty or modified gene is reintroduced to a living population in order to instigate a controlled disruption to a target species’ VGT cycle – has been proposed as an effective means of controlling local populations (or entire species) of pests in an “environmentally-friendly” manner. In essence, faulty, or modified versions of genes, known as alleles, are ‘cut and pasted’ into the genomes of many ‘carrier’ organisms within a target species’ population. When carriers mate, they will distribute these alleles via VGT to any subsequent progeny, with offspring that inherit two copies of this modified gene becoming either sterile, or failing to develop beyond specific embryonic stages. The few initial investigations conducted on Gene Drives using CRISPR [on paper] have indicated the approach may effectively distort the breeding of targeted species by weaponizing their own inheritable genetic materials to undermine the viability of any subsequent offspring (essentially, sabotaging the population of VGT offspring resulting directly from the genetically modified parents). However, ‘homing’ endonuclease enzymes, that typically act on sequence errors and damage in DNA structures, could alter or repair ‘pasted’ segments in DNA; plausibly creating a biological resistance to gene drives, requiring biocontrol measures to implement multiple coinciding ‘edits’ at the same time.

In spite of early preliminary success (mostly for efficiency, not safety) in closed settings, bioethicists have raised well-founded concerns over the wider implementation of gene drives, and challenged the broader adoption of these genetic engineering technologies due to several outstanding, pervasive issues which we simply do not possess robust scientific observations for at present. Authorities in the discipline (mostly from ecological/ conservation camps, as opposed to technology contributors) have already indicated that ‘rouge gene drives’ are already capable of impacting broader biotic networks outside of the intended target vector. Some of the pertinent issues already raised include; whether mid-drive mutations may affect the expression of a modified gene, or enable it to be carried forward beyond an intended ‘closed-loop’ generational target; whether hybridisation may transfer the distortive gene outside of a targeted genetic pool; and also whether the intended target population may itself spread this modified genetic material to non-targeted population centres of a species. Certainly, some gene drive advocates have already made arguments to justify the extinction of an entire ‘pest’ species, but purposeful acts need to be openly debated beforehand. Further, while gene drives are intended to purposefully function only on a target species, the effective causality and range of it’s changes in a living ecosystem will inevitably lead to side effects – for instance, organisms that naturally predate on the target species may be impacted by a lack of prey, peripheral symbiotic networks that avail of the ‘pest’ species may be unable to utilise their biological services, or another unintended species may arise to fill the vacated niche to devastating effect (as seen in the aftermath of chemical spraying campaigns). Inventing synthetic changes to the genetic materials of organisms may also open the doorway for nature to blindly make changes that were previously unavailable to evolution. Regardless, it is highly likely that gene drive technologies will find a way to intertwine the fates of entire ecological webs to catastrophic effect if given enough time to imbed change in a pre-established, evolving environmental setting. The delayed risks over immediate rewards need finer balancing, as gene drives may become the very thing they are being designed to fight: invasive or pest species.

Given the mainstream societal interest in pre-emptively funding the widespread development and implementation of genetic engineering technologies across a plethora of economic sectors, a diverse array of scientists recently established the Global Observatory for Genome Editing to foster international, interdisciplinary, and cross-sectoral dialogue on the moral, ethical and democratic perspectives governing the modification of all life's inheritable genetic materials. Understanding the broad range of contributing disciplinary perspectives which feed into this socio-bio-technological enterprise is, perhaps, one of the most fundamental pillars we should utilise in chartering any way forward with any genetic engineering – or not – but, in the very least, such inclusive and far-reaching deliberations should be the hallmark of an intelligent species before translating decisions into potentially unretractable acts across ecosystems. As proponents of the Observatory also surmise about genome editing; “Technologies are poised to alter the meaning of being human”, therefore it is crucial to openly discuss the many fundamental questions now arising with these ever-advancing technologies before the genetic material of all future life is folded into the human material domain – a possession we must inherently pass on to those not yet born. This is not a genetic ‘purism’ argument, but rather a cautionary tale in technological advancement without oversight; one that will be written in the fabric of life, and in context with our 'conservation' of Earth over the past century.

As part of the After the Horizon library, and our contribution towards retaining the memory of essential information in this particular field, the Beyond the Earth foundation is facilitating the development of an archival resource intent on documenting the diverse array of purposeful genetic changes which are steadily being introduced across various ecosystems for a variety applications, including; pest vector control campaigns, ‘improving’ agricultural products yields, and (where documentation exists) the unauthorised release of GMOs for controlled settings. As with the capability of POPs to transcend local national boundaries, GMOs (purposely manufactured and released, or unintentionally ‘orphaned’ genomes) in any natural environment are not geographically restricted, and therefore, will likely spread throughout available ecological niches. Therefore, this catalogue intends to simply document the various GMOs purposefully introduced to environmental settings, detailing properties such as the technical parameters behind the gene edits, intended target species, desired outcomes, and release procedures, alongside other justifications and cautionary measures that received satisfactory approval in biosafety standards from GMO regulating authorities.

Notes to catalogue: The diverse catalogue contents are compiled through peer-reviewed academic studies, third-party literature, and international journalist investigations, in addition to occasional freedom of information requests. As such (and given the relatively nascent nature of GMO legacies we are still only beginning to encounter), it is acknowledged this catalogue is an active document, subject to updates, amendments, and peer-review. While the foundation is not directly engaged with the moral and ethical arguments concerning GM applications, we advocate that humanity should continue to err on the side of precaution when initiating profound changes across our biome in the absence of any reliable knowledge on the long-term consequences of these modifications. We may also find that contemplating these long-delayed challenges for life under the precautionary principle, and provisional scenario planning, can also help contemporary generations to understand our growing reach throughout the ages, and enable us to build resilience to the anticipated outcomes, or envisioned crises, over time using long-term planning. Further to these contemporary benefits, peering far-far forward in time, after the horizon, may also contribute valuable insights useful for the establishment of long-term organised human societies, while creating new behavioural concepts, and planning strategies that may prove beneficial for future intergenerational studies of GMOs.

Page last updated: 19 Jan 2022