Scholarly Literature

This is a database of scholarly literature that concentrates currently on natural and engineered selfish genetic elements (gene drives).  The latest are shown here.
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A spatially discrete, integral projection model and its application to invasive carp

11503
R. A. Erickson, E. A. Eager, P. M. Kocovsky, D. C. Glover, J. L. Kallis and K. R. Long,  Ecological Modelling,  387:163-171. 2018-09-21 20:46:26.
Natural resource managers and ecologists often desire an understanding of spatial dynamics such as migration, dispersion, and meta-population dynamics. Network-node models can capture these salient features. Additionally, the state-variable used with many species may be appropriately modeled as a continuous variable (e.g., length) and management activities sometimes can only target individuals of certain sizes. Integral projection models (IPMs) can capture this life history characteristic and allow for the examination of size-specific management. We combined an IPM with a network-node model to capture both of these salient features. We then demonstrated how this model could be used to understand and manage populations of invasive species focusing on grass carp as an example. Grass carp disrupt ecosystems outside of their native range and have spread around much of the world, including North America. The impacts of grass carp include adversely changing aquatic plant communities, which in turn affect a wide range of endpoints ranging from water quality to waterfowl recruitment. We specifically examined two theoretical systems using parameters from the literature. First, we modeled a lake with two tributaries and examined how modified sterile males could be used as a control tool. We found that modified sterile males may be a feasible control tool to limit population growth. Second, we modeled a series of river pools and examined how harvest and deterrents could be used to decrease the risk of expanding grass carp's range within a river system. Within this system, we also compared the impacts of size specific harvest and uniform harvest across all sizes. We found that targeting the largest, spawning populations may be more important than targeting the populations close to the invasion front for reducing the risk of spreading grass carp. We also demonstrate that size of harvested fish was important for controlling populations.

Pest demography critically determines the viability of synthetic gene drives for population control

11505
K. E. Wilkins, T. A. A. Prowse, P. Cassey, P. Q. Thomas and J. V. Ross,  Mathematical Biosciences,  305:160-169. 2018-09-13 20:48:39.
Synthetic gene drives offer a novel solution for the control of invasive alien species. CRISPR-based gene drives can positively bias their own inheritance, and comprise a DNA sequence that is replicated by homologous recombination. Since gene drives can be positioned to silence fertility or developmental genes, they could be used for population suppression. However, the production of resistant alleles following self-replication errors threatens the technology's viability for pest eradication in real-world applications. Further, a robust assessment of how pest demography impacts the expected progression of gene drives through populations is currently lacking. We used a deterministic, two-sex, birth-death model to investigate how demographic assumptions affect the efficiency of suppression drives for controlling invasive rodents on islands, for two different gene-drive strategies. We show that mass-action reproduction results in overly optimistic eradication outcomes when compared to the more realistic assumption of polygynous breeding. When polygyny was assumed, both gene-strategies failed due to the evolution of resistance unless a reproductive Allee effect (reduced reproductive rates at low population density) was also included; although model outcomes were highly sensitive to the strength of this effect. Increasing the size of the initial gene-drive introduction (up to 10% of carrying capacity) had little impact on population outcomes. Understanding the demography of a population targeted for eradication is critical before the viability of gene-drive suppression can be adequately assessed.

A sustainable synthetic biology approach for the control of the invasive golden mussel (Limnoperna fortunei)

19204
M. F. Rebelo, L. F. Afonso, J. A. Americo, L. da Silva, J. L. B. Neto, F. Dondero and Q. Zhang,  PeerJ Preprints,  6:e27164v3. 2018-09-12 14:52:07.
The recent development of the CRISPR-Cas9-based gene drive has created the conditions to seriously consider this technology to solve one of the major environmental challenges in biodiversity conservation i.e. the control of invasive species. There is no efficient control method for golden mussel infestation available so far. Here we discuss the technical and economic feasibility of using a synthetic biology based approach to fight and control the invasive mussel Limnoperna fortunei in South American rivers and reservoirs.

Sex determination in Neotropical fish: Implications ranging from aquaculture technology to ecological assessment

11495
J. I. Fernandino and R. S. Hattori,  General and Comparative Endocrinology,  273:172-183. 2018-07-07 20:24:06.
The high biodiversity of fish in the Neotropical region contrasts with scarce or biased studies on the mechanisms involved in the sex determination in members of this fauna. In this review, we attempted to compile the information available on determination, differentiation, and manipulation of sex for Neotropical species, with special focus on silversides and other two speciose groups, known as characins (Characiformes) and catfishes (Siluriformes). Currently, there is plenty of information available on chromosomal sex determination systems, which includes both male and female heterogamety with many variations, and sex chromosomes evolution at the macro chromosomal level. However, there is hitherto a blank in information at micro, gene/molecule levels and in research related to the effects of environmental cues on sex determination; most of reported studies are limited to silversides and guppies. In view of such a high diversity, it is critically necessary to establish key model species for relevant Neotropical fish taxa and also multi-disciplinary research groups in order to uncover the main patterns and trends that dictate the mechanisms of sex determination and gonadal differentiation in this icthyofauna. By increasing our knowledge on sex determination/differentiation with the identification of sex chromosome-linked markers or sex-determining genes, characterization of the onset timing of morphological gonadal differentiation, and determination of the environmental-hormonal labile period of gonadal sex determination in reference species, it will be possible to use those information as guidelines for application in other related groups. Overall, the strategic advance in this research field will be crucial for the development of biotechnological tools for aquaculture industry and for conservation of fish fauna from the Neotropical Region.

Global report on insecticide resistance in malaria vectors: 2010-2016.

12683
WHO,  World Health Organization,  2018-05-01 18:13:11.
Insecticide-based vector control is a cornerstone in the fight against malaria. Selection of vector-control interventions should take into account the resistance status of local mosquito vectors along with other factors associated with intervention deployment and use such as availability, cost and cost -effectiveness as well as population acceptance or compliance. Strategic insecticide resistance monitoring is therefore essential to inform evidence-based vector control.

Genetics-based methods for agricultural insect pest management

18687
N. Alphey and M. B. Bonsall,  Agricultural and Forest Entomology,  20:131-140. 2018-05-01 13:30:37.
Abstract The sterile insect technique is an area-wide pest control method that reduces agricultural pest populations by releasing mass-reared sterile insects, which then compete for mates with wild insects. Contemporary genetics-based technologies use insects that are homozygous for a repressible dominant lethal genetic construct rather than being sterilized by irradiation. Engineered strains of agricultural pest species, including moths such as the diamondback moth Plutella xylostella and fruit flies such as the Mediterranean fruit fly Ceratitis capitata, have been developed with lethality that only operates on females. Transgenic crops expressing insecticidal toxins are widely used; the economic benefits of these crops would be lost if toxin resistance spread through the pest population. The primary resistance management method is a high-dose/refuge strategy, requiring toxin-free crops as refuges near the insecticidal crops, as well as toxin doses sufficiently high to kill wild-type insects and insects heterozygous for a resistance allele. Mass-release of toxin-sensitive engineered males (carrying female-lethal genes), as well as suppressing populations, could substantially delay or reverse the spread of resistance. These transgenic insect technologies could form an effective resistance management strategy. We outline some policy considerations for taking genetic insect control systems through to field implementation.

One prophage WO gene rescues cytoplasmic incompatibility in Drosophila melanogaster

5926
Shropshire, J. D., J. On, E. M. Layton, H. Zhou and S. R. Bordenstein,  Proceedings of the National Academy of Sciences,  115:4987. 2018-04-23 16:58:30.
The World Health Organization recommended pilot deployment of Wolbachia-infected mosquitoes to curb viral transmission to humans. Releases of mosquitoes are underway worldwide because Wolbachia can block replication of these pathogenic viruses and deterministically spread by a drive system termed cytoplasmic incompatibility (CI). Despite extensive research, the underlying genetic basis of CI remains only half-solved. We recently reported that two prophage WO genes recapitulate the modification component of CI in a released strain for vector control. Here we show that one of these genes underpins rescue of CI. Together, our results reveal the complete genetic basis of this selfish trait and pave the way for future studies exploring WO prophage genes as adjuncts or alternatives to current control efforts.Wolbachia are maternally inherited, intracellular bacteria at the forefront of vector control efforts to curb arbovirus transmission. In international field trials, the cytoplasmic incompatibility (CI) drive system of wMel Wolbachia is deployed to replace target vector populations, whereby a Wolbachia-induced modification of the sperm genome kills embryos. However, Wolbachia in the embryo rescue the sperm genome impairment, and therefore CI results in a strong fitness advantage for infected females that transmit the bacteria to offspring. The two genes responsible for the wMel-induced sperm modification of CI, cifA and cifB, were recently identified in the eukaryotic association module of prophage WO, but the genetic basis of rescue is unresolved. Here we use transgenic and cytological approaches to demonstrate that maternal cifA expression independently rescues CI and nullifies embryonic death caused by wMel Wolbachia in Drosophila melanogaster. Discovery of cifA as the rescue gene and previously one of two CI induction genes establishes a “Two-by-One” model that underpins the genetic basis of CI. Results highlight the central role of prophage WO in shaping Wolbachia phenotypes that are significant to arthropod evolution and vector control.

The ethical implications of population suppression and the irreversibility of gene drives

14167
J. Kim,  International Journal of Life Sciences Research,  2018-04-01 14:11:25.
This paper aims to examine the current situation by presenting important ethical arguments that include Chardin’s principle of irreversibility and Weiss’ beliefs on intergenerational equity, ideals upheld by the United Nations

Transgenic Mosquitoes – Fact or Fiction?

5907
Wilke, A. B. B., J. C. Beier and G. Benelli,  Trends in Parasitology,  34:456-465. 2018-03-08 16:14:34.
echnologies for controlling mosquito vectors based on genetic manipulation and the release of genetically modified mosquitoes (GMMs) are gaining ground. However, concrete epidemiological evidence of their effectiveness, sustainability, and impact on the environment and nontarget species is lacking; no reliable ecological evidence on the potential interactions among GMMs, target populations, and other mosquito species populations exists; and no GMM technology has yet been approved by the WHO Vector Control Advisory Group. Our opinion is that, although GMMs may be considered a promising control tool, more studies are needed to assess their true effectiveness, risks, and benefits. Overall, several lines of evidence must be provided before GMM-based control strategies can be used under the integrated vector management framework.

Population modification of Anopheline species to control malaria transmission

6694
R. Carballar-Lejarazú and A. A. James,  Pathogens and Global Health,  111:424-435. 2018-02-01 17:58:10.
Vector control strategies based on population modification of Anopheline mosquitoes may have a significant role in the malaria eradication agenda. They could consolidate elimination gains by providing barriers to the reintroduction of parasites and competent vectors, and allow resources to be allocated to new control sites while maintaining treated areas free of malaria. Synthetic biological approaches are being used to generate transgenic mosquitoes for population modification. Proofs-of-principle exist for mosquito transgenesis, the construction of anti-parasite effector genes and gene-drive systems for rapidly introgressing beneficial genes into wild populations. Key challenges now are to develop field-ready strains of mosquitoes that incorporate features that maximize safety and efficacy, and specify pathways from discovery to development. We propose three pathways and a framework for target product profiles that maximize safety and efficacy while meeting the demands of the complexity of malaria transmission, and the regulatory and social diversity of potential end-users and stakeholders.

Gene drives and the management of agricultural pests

13810
R. F. Medina,  Journal of Responsible Innovation,  5:S255-S262. 2018-01-24 16:01:13.
Like all pest control strategies, gene drives are not hazard-free. Ecological risk assessment of gene drives designed to control agricultural pests should be conducted before their deployment. The present commentary provides some thoughts on some of the issues one should consider when contemplating using gene drives in the management of agricultural pests.

Summary

13808
Committee on Gene Drive Research in Non-Human Organisms: Recommendations for Responsible,  Journal of Responsible Innovation,  5:S243-S254. 2018-01-24 15:58:19.
Scientists have studied gene drives for more than 50 years. The development of a powerful genome editing tool in 2012, CRISPR/Cas9,1 led to recent breakthroughs in gene drive research that built on that half century’s worth of knowledge, and stimulated new discussion of the potential applications and implications of gene drive technologies.

Anomaly handling and the politics of gene drives

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S. W. Evans and M. J. Palmer,  Journal of Responsible Innovation,  5:S223-S242. 2018-01-24 15:56:09.
Decisions about the development and use of gene drives are framing broader debates about the need for fundamental changes to biotechnology regulatory systems. We summarize this debate and describe how gene drives are being constructed as potential anomalies within the regulatory landscape.

Regulating animals with gene drive systems: lessons from the regulatory assessment of a genetically engineered mosquito

13804
Z. Meghani and J. Kuzma,  Journal of Responsible Innovation,  5:S203-S222. 2018-01-24 15:52:57.
In this paper, we consider the question of whether the United States Food and Drug Administration is prepared to effectively regulate insects and other animals with gene drives. Given the profound impact that gene drives could have on species and ecosystems, their use is a highly contentious issue. The rigorous regulation of insects and other animals with gene drive systems is crucial.

Developing gene drive technologies to eradicate invasive rodents from islands

13798
C. M. Leitschuh, D. Kanavy, G. A. Backus, R. X. Valdez, M. Serr, E. A. Pitts, D. Threadgill and J. Godwin,  Journal of Responsible Innovation,  5:S121-S138. 2018-01-24 15:45:57.
Gene drive methods of rodent eradication offer an alternative to killing that has the potential to be more species-specific, more humane, and more biologically safe for use around humans. Implementing this technology would involve releasing laboratory-developed engineered mice into wild populations. Some areas for further research include assessing the ecological effects of releasing engineered mice, the potential risks for the accidental or deliberate release of genetically modified organisms into mainland mouse populations, and the social, ethical, and regulatory acceptability of the technology.

Agricultural production: assessment of the potential use of Cas9-mediated gene drive systems for agricultural pest control

13796
M. J. Scott, F. Gould, M. Lorenzen, N. Grubbs, O. Edwards and D. O’Brochta,  Journal of Responsible Innovation,  5:S98-S120. 2018-01-24 15:43:20.
To highlight how gene drives could be useful for control of agricultural insect pests, we selected species that are pests of animals (New World screwworm), plants (spotted wing Drosophila, diamondback moth, Bemisia tabaci whitefly), or stored grains (red flour beetle). We provide examples of gene drives that target specific genes including female-essential genes. Further, we discuss issues related to containment in the laboratory and eventual field testing of strains harboring a Cas9-mediated gene drive system.

A roadmap for gene drives: using institutional analysis and development to frame research needs and governance in a systems context

13790
J. Kuzma, F. Gould, Z. Brown, J. Collins, J. Delborne, E. Frow, K. Esvelt, D. Guston, C. Leitschuh, K. Oye and S. Stauffer,  Journal of Responsible Innovation,  5:S13-S39. 2018-01-24 15:34:37.
This paper reports on a workshop held in February 2016 to explore the complex intersection of political, economic, ethical, and ecological risk issues associated with gene drives. Workshop participants were encouraged to use systems thinking and mapping to describe the connections among social, policy, economic, and ecological variables as they intersect within governance systems. In this paper, we analyze the workshop transcripts and maps using the Institutional Analysis and Development (IAD) framework to categorize variables associated with gene drive governance and account for the complexities of socio-ecological systems.

Mapping research and governance needs for gene drives

13788
J. Delborne, J. Kuzma, F. Gould, E. Frow, C. Leitschuh and J. Sudweeks,  Journal of Responsible Innovation,  5:S4-S12. 2018-01-24 15:28:09.
This special issue represents both deep and broad thinking about gene drives. The papers were first drafted nearly two years ago, and since then have been reviewed and revised to flesh out key arguments and take account of ongoing developments in the field. This field has moved very fast indeed! Technical research publications have increased in number; NASEM released a major report in June 2016; and workshops have proliferated.

Gene drives and the expanding horizon of governance

13786
E. Fisher,  Journal of Responsible Innovation,  5:S1-S3. 2018-01-24 15:23:59.
Like other areas of emerging science and technology that trigger prolonged public debate over their transformative prospects, gene drives simultaneously generate prospects for new knowledge, hoped-for benefits, and formidable concerns. Their ability to bias inheritance of and in theory spread a genetic trait throughout an entire population of organisms—even to the point of extinction—is driving home the need for their responsible governance. Significantly, it is also driving home the need to develop capacities for such governance.

A Framework for the risk assessment and management of gene drive technology in contained use

4023
van der Vlugt, CJBB, David D.; Lehmann, Kathleen; Leunda, Amaya; Willemarck, Nicolas,  Applied Biosafety,  23:25-31. 2018-01-21 00:00:00.
The utilisation of the CRISPR/Cas9 technology has sparked a renewed interest in gene drive mechanisms. These mechanisms of biased inheritance may yield promising applications in the fields of vector control and nature conservation. However, the same properties that will enable these applications may also pose a risk if organisms that are equipped with gene drive cassettes are unintentionally released into the environment. Although several groups of scientists and regulators have started to address these safety concerns, there are currently no dedicated guidelines published on the required risk assessment and minimal control measures applicable to gene drive organisms in contained use. To fill this gap, this paper describes a fundamental approach to assessing the risks of these organisms while handled in a contained laboratory environment. Based on the likelihood that an adverse effect will arise from the handling of a gene drive organism and the severity of this effect, three risk classes for contained use activities are presented. Finally, specific minimum requirements regarding physical measures and working practices are proposed according to the presented risk classes and tailored to activities with rodents, insects, and fungi, which are most likely to be used for gene drive applications in the near future.

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