Featured Articles
Incorporating ecology into gene drive modelling
28150J. Kim, K. D. Harris, I. K. Kim, S. Shemesh, P. W. Messer and G. Greenbaum, Ecology Letters, 26:S62-S80. 2023-10-23 11:37:54.
Abstract Gene drive technology, in which fast-spreading engineered drive alleles are introduced into wild populations, represents a promising new tool in the fight against vector-borne diseases, agricultural pests and invasive species. Due to the risks involved, gene drives have so far only been tested in laboratory settings while their population-level behaviour is mainly studied using mathematical and computational models. The spread of a gene drive is a rapid evolutionary process that occurs over timescales similar to many ecological processes. This can potentially generate strong eco-evolutionary feedback that could profoundly affect the dynamics and outcome of a gene drive release. We, therefore, argue for the importance of incorporating ecological features into gene drive models. We describe the key ecological features that could affect gene drive behaviour, such as population structure, life-history, environmental variation and mode of selection. We review previous gene drive modelling efforts and identify areas where further research is needed. As gene drive technology approaches the level of field experimentation, it is crucial to evaluate gene drive dynamics, potential outcomes, and risks realistically by including ecological processes.
Millions of Mosquitoes Will Rain Down on Hawaii to Save an Iconic Bird
28010S. Wild, Scientific American, 2023-10-06 06:53:13.
Millions of mosquitoes dropped from helicopters could be the greatest hope for Hawaii’s iconic honeycreepers. At least four species of the brightly colored birds could go extinct within the year if no action is taken to save them. “We’re seriously in a race against time at the moment,” says Hanna Mounce, program manager of the Maui Forest Bird Recovery Project. These small birds evolved on the islands over the course of millions of years and are uniquely adapted to their niche habitat, where they are crucial pollinators for many of Hawaii’s flora. For the people of Hawaii, the honeycreepers are also woven into the cultural fabric, featuring prominently in many legends and providing feathers for traditional garments. More than 50 species of honeycreepers once flitted across the archipelago, but because of introduced predators, habitat destruction and disease, that number has dwindled to only 17. Invasive Culex quinquefasciatus mosquitoes—possibly introduced via water barrels on European ships in the early 19th century—pose a particular threat because they spread the deadly avian malaria parasite.IIT works like this: C. quinquefasciatus mosquitoes, as well as many other arthropods, naturally contain Wolbachia bacteria in their gut. In order to produce offspring together, mating mosquitoes must be infected with the same strain of the bacteria. Birds, Not Mosquitoes’ plan involves releasing male mosquitoes bred by Verily Life Sciences—the life sciences research arm of Alphabet, which also owns Google. These mosquitos will host a different Wolbachia strain than those on Maui. The idea is that the existing female mosquitoes will mate with the male newcomers, but because of their incompatible Wolbachia bacteria, they will not produce viable offspring. If all goes according to plan, the overall mosquito population will plummet.
Measuring the Impact of Genetic Heterogeneity and Chromosomal Inversions on the Efficacy of CRISPR-Cas9 Gene Drives in Different Strains of Anopheles gambiae
27837Pescod, Poppy Bevivino, Giulia Anthousi, Amalia Shelton, Ruth Shepherd, Josephine Lombardo, Fabrizio Nolan, Tony, The CRISPR Journal, 2023-09-13 09:06:32.
The human malaria vector Anopheles gambiae is becoming increasingly resistant to insecticides, spurring the development of genetic control strategies. CRISPR-Cas9 gene drives can modify a population by creating double-stranded breaks at highly specific targets, triggering copying of the gene drive into the cut site (?homing?), ensuring its inheritance. The DNA repair mechanism responsible requires homology between the donor and recipient chromosomes, presenting challenges for the invasion of laboratory-developed gene drives into wild populations of target species An. gambiae species complex, which show high levels of genome variation. Two gene drives (vas2-5958 and zpg-7280) were introduced into three An. gambiae strains collected across Africa with 5.3?6.6% variation around the target sites, and the effect of this variation on homing was measured. Gene drive homing across different karyotypes of the 2La chromosomal inversion was also assessed. No decrease in gene drive homing was seen despite target site heterology, demonstrating the applicability of gene drives to wild populations.
Gene drives for invasive wasp control: Extinction is unlikely, with suppression dependent on dispersal and growth rates
27669P. J. Lester, D. O'Sullivan and G. L. W. Perry, Ecological Applications, 2023-08-24 06:36:30.
Abstract Gene drives offer a potentially revolutionary method for pest control over large spatial extents. These genetic modifications spread deleterious variants through a population and have been proposed as methods for pest suppression or even eradication. We examined the influence of local dispersal, long-distance and/or human-mediated dispersal, and variation in population growth, on the success of a gene drive for the control of invasive social wasps (Vespula vulgaris). Our simulations incorporated a spatially realistic environment containing variable habitat quality in New Zealand. Pest eradication was not observed, except in extreme and unrealistic scenarios of constant, widespread, and spatially intense releases of genetically modified individuals every year for decades. Instead, the regional persistence of genetically modified and wild-type wasps was predicted. Simulations using spatially homogeneous versus realistic landscapes (incorporating uninhabitable areas and dispersal barriers) showed little difference in overall population dynamics. Overall, little impact on wasp abundance was observed in the first 15?years post-introduction. After 25?years, populations were suppressed to levels <95% of starting populations. Populations exhibited ?chase dynamics? with population cycles in space, with local extinction occurring in some areas while wasps became abundant in others. Increasing the wasps' local dispersal distance increased the spatial and temporal variability of the occupied area and population suppression. Varying levels of human-associated long-distance dispersal had little effect on population dynamics. Increasing intrinsic population growth rates interacted with local dispersal to cause higher mean populations and substantially higher levels of variation in population suppression and the total amount of landscape occupied. Gene drives appear unlikely to cause a rapid and widespread extinction of this and probably other pests, but could offer long-term and cost-effective methods of pest suppression. The predicted level of <95% pest suppression would substantially reduce the predation pressure and competitive interactions of this invasive wasp on native species. However, the predicted long-term persistence of genetically modified pests will influence the ethics and likelihood of using gene drives for pest control, especially given concerns that modified wasps would eventually be transported back to their home range.
Single-cell profiling of Anopheles gambiae spermatogenesis defines the onset of meiotic silencing and premeiotic overexpression of the X chromosome
27624N. Page, C. Taxiarchi, D. Tonge, J. Kuburic, E. Chesters, A. Kriezis, K. Kyrou, L. Game, T. Nolan and R. Galizi, Commun Biol, 6:850. 2023-08-15 10:04:13.
Understanding development and genetic regulation in the Anopheles gambiae germline is essential to engineer effective genetic control strategies targeting this malaria mosquito vector. These include targeting the germline to induce sterility or using regulatory sequences to drive transgene expression for applications such as gene drive. However, only very few germline-specific regulatory elements have been characterised with the majority showing leaky expression. This has been shown to considerably reduce the efficiency of current genetic control strategies, which rely on regulatory elements with more tightly restricted spatial and/or temporal expression. Meiotic silencing of the sex chromosomes limits the flexibility of transgene expression to develop effective sex-linked genetic control strategies. Here, we build on our previous study, dissecting gametogenesis into four distinct cell populations, using single-cell RNA sequencing to define eight distinct cell clusters and associated germline cell-types using available marker genes. We reveal overexpression of X-linked genes in a distinct cluster of pre-meiotic cells and document the onset of meiotic silencing of the X chromosome in a subcluster of cells in the latter stages of spermatogenesis. This study provides a comprehensive dataset, characterising the expression of distinct cell types through spermatogenesis and widening the toolkit for genetic control of malaria mosquitoes.
Proposed Changes to the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines)
27609National Institutes of Health, Federal Register, 2023-08-10 08:09:09.
The National Institutes of Health (NIH) seeks input on a proposal to revise the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (NIH Guidelines) to include specific considerations and requirements for conducting research involving gene drive modified organisms (GDMO) in contained research settings. NIH is proposing to update the NIH Guidelines to clarify minimum containment requirements, propose considerations for performing risk assessments, and define additional institutional responsibilities regarding Institutional Biosafety Committees (IBCs) and Biosafety Officers (BSOs). The proposed revisions are specific to GDMO research subject to the NIH Guidelines, conducted in contained settings and are consistent with the recommendations of the NIH Novel and Exceptional Technology Research Advisory Committee report, Gene Drives in Biomedical Research (NExTRAC Report). NIH does not currently support research involving potential field release of GDMOs and the NIH Guidelines pertain to contained research; accordingly, no changes regarding potential field release are being proposed in this Notice. NIH is also proposing revisions to the NIH Guidelines to harmonize with the Biosafety in Microbiological and Biomedical Laboratories (BMBL), 6th edition regarding the Risk Group (RG) categorization of West Nile Virus (WNV) and Saint Louis Encephalitis Virus (SLEV).
wMel replacement of dengue-competent mosquitoes is robust to near-term change
27584V. N. Vásquez, L. M. Kueppers, G. Rašić and J. M. Marshall, Nature Climate Change, 13:848-855. 2023-08-01 08:16:33.
Rising temperatures are impacting the range and prevalence of mosquito-borne diseases. A promising biocontrol technology replaces wild mosquitoes with those carrying the virus-blocking Wolbachia bacterium. Because the most widely used strain, wMel, is adversely affected by heat stress, we examined how global warming may influence wMel-based replacement. We simulated interventions in two locations with successful field trials using Coupled Model Intercomparison Project Phase 5 climate projections and historical temperature records, integrating empirical data on wMel’s thermal sensitivity into a model of Aedes aegypti population dynamics to evaluate introgression and persistence over one year. We show that in Cairns, Australia, climatic futures necessitate operational adaptations for heatwaves exceeding two weeks. In Nha Trang, Vietnam, projected heatwaves of three weeks and longer eliminate wMel under the most stringent assumptions of that symbiont’s thermal limits. We conclude that this technology is generally robust to near-term (2030s) climate change. Accelerated warming may challenge this in the 2050s and beyond.
Cost-effectiveness of Precision Guided SIT for Control of Anopheles gambiae in the Upper River Region, The Gambia
27060G. William, R. Robyn, M. Agastya, M. S. C. Hector, S. Andrea, Z. David, G. I. Patrick, D. Umberto, Alessandro, M. M. John and A. Omar, bioRxiv, 2023.07.20.549762. 2023-07-22 06:41:45.
Precision-guided sterile insect technique (pgSIT) is an extremely promising vector control intervention that can reduce and potentially eliminate the unacceptable malaria burden, particularly in sub-Saharan Africa. Here we explore the cost effectiveness of using this approach in Africa using mathematical modeling and economical analysis. Overall, we find that pgSIT represents a cost-effective and promising approach to A. gambiae control in The Gambia, with the potential to deliver significant economic and social benefits.Competing Interest StatementThis work was supported by funding from an Open Philanthropy award (309937-0001). The views, opinions, and/or findings expressed are those of the authors and should not be interpreted as representing the official views or policies of the U.S. government. Figures were created using www.BioRender.com.
Dual effector population modification gene-drive strains of the African malaria mosquitoes, Anopheles gambiae and Anopheles coluzzii
26580R. Carballar-Lejarazú, Y. Dong, T. B. Pham, T. Tushar, R. M. Corder, A. Mondal, H. M. Sánchez C, H.-F. Lee, J. M. Marshall, G. Dimopoulos and A. A. James, Proceedings of the National Academy of Sciences, 120:e2221118120. 2023-07-11 05:52:31.
Proposed genetic approaches for reducing human malaria include population modification, which introduces genes into vector mosquitoes to reduce or prevent parasite transmission. We demonstrate the potential of Cas9/guide RNA (gRNA)?based gene-drive systems linked to dual antiparasite effector genes to spread rapidly through mosquito populations. Two strains have an autonomous gene-drive system coupled to dual anti-Plasmodium falciparum effector genes comprising single-chain variable fragment monoclonal antibodies targeting parasite ookinetes and sporozoites in the African malaria mosquitoes Anopheles gambiae (AgTP13) and Anopheles coluzzii (AcTP13). The gene-drive systems achieved full introduction within 3 to 6 mo after release in small cage trials. Life-table analyses revealed no fitness loads affecting AcTP13 gene-drive dynamics but AgTP13 males were less competitive than wild types. The effector molecules reduced significantly both parasite prevalence and infection intensities. These data supported transmission modeling of conceptual field releases in an island setting that shows meaningful epidemiological impacts at different sporozoite threshold levels (2.5 to 10 k) for human infection by reducing malaria incidence in optimal simulations by 50 to 90% within as few as 1 to 2 mo after a series of releases, and by ≥90% within 3 mo. Modeling outcomes for low sporozoite thresholds are sensitive to gene-drive system fitness loads, gametocytemia infection intensities during parasite challenges, and the formation of potentially drive-resistant genome target sites, extending the predicted times to achieve reduced incidence. TP13-based strains could be effective for malaria control strategies following validation of sporozoite transmission threshold numbers and testing field-derived parasite strains. These or similar strains are viable candidates for future field trials in a malaria-endemic region.
Nuclear Technique Used in Europe for First time to Battle Yellow Fever Mosquito Found in Cyprus
26314IAEA, IAEA, 2023-06-27 07:43:22.
Cyprus this month released the first batch of 100,000 sterile mosquitos to begin the implementation of a Food and Agriculture Organization (FAO) and International Atomic Energy Agency (IAEA) project testing the use of a nuclear technique to eradicate an invasive species of mosquitoes found in the country.Cyprus confirmed the presence of the Aedes aegypti mosquito, also called Yellow Fever mosquito, on the island in 2022. This species of mosquito can carry serious vector-borne diseases such as chikungunya, dengue, yellow fever and Zika. The Aedes albopictus - also a carrier for such diseases - was also confirmed to be present on the island in 2022. Vector-borne diseases cause over 700,000 global deaths per year and the presence of the two species poses an immediate threat to Cyprus’ economy and healthcare system in case of a disease outbreak.
Draft environmental assessment for use of Wolbachia-based incompatible insect technique for the suppression of nonnative southern house mosquito populations on Kauaʻi
26247Hawai'i Department of Land and Natural Resources, Hawai'i Department of Land and Natural Resources, 2023-06-16 07:31:10.
The State of Hawai'i Department of Land and Natural Resources hereby transmits the Draft Environmental Assessment and Anticipated Finding of No Significant Impact (DEAEnvironmental Assessment for use of Wolbachia-based Incompatible Insect Technique for the suppression of nonnative southern house mosquito populations o Kaua'i to be published in the next available edition of The Environmental Notice.
CRISPR/Cas9-based split homing gene drive targeting doublesex for population suppression of the global fruit pest Drosophila suzukii
25710A. K. Yadav, C. Butler, A. Yamamoto, A. A. Patil, A. L. Lloyd and M. J. Scott, Proc Natl Acad Sci U S A, 120:e2301525120. 2023-06-13 10:38:33.
Genetic-based methods offer environmentally friendly species-specific approaches for control of insect pests. One method, CRISPR homing gene drive that target genes essential for development, could provide very efficient and cost-effective control. While significant progress has been made in developing homing gene drives for mosquito disease vectors, little progress has been made with agricultural insect pests. Here, we report the development and evaluation of split homing drives that target the doublesex (dsx) gene in Drosophila suzukii, an invasive pest of soft-skinned fruits. The drive component, consisting of dsx single guide RNA and DsRed genes, was introduced into the female-specific exon of dsx, which is essential for function in females but not males. However, in most strains, hemizygous females were sterile and produced the male dsx transcript. With a modified homing drive that included an optimal splice acceptor site, hemizygous females from each of the four independent lines were fertile. High transmission rates of the DsRed gene (94 to 99%) were observed with a line that expressed Cas9 with two nuclear localization sequences from the D. suzukii nanos promoter. Mutant alleles of dsx with small in-frame deletions near the Cas9 cut site were not functional and thus would not provide resistance to drive. Finally, mathematical modeling showed that the strains could be used for suppression of lab cage populations of D. suzukii with repeated releases at relatively low release ratios (1:4). Our results indicate that the split CRISPR homing gene drive strains could potentially provide an effective means for control of D. suzukii populations.
Molecular Biology of Cytoplasmic Incompatibility Caused by Wolbachia Endosymbionts
25549M. Hochstrasser, Annual Review of Microbiology, 2023-06-07 08:38:45.
Among endosymbiotic bacteria living within eukaryotic cells, Wolbachia is exceptionally widespread, particularly in arthropods. Inherited through the female germline, it has evolved ways to increase the fraction of bacterially infected offspring by inducing parthenogenesis, feminization, male killing, or, most commonly, cytoplasmic incompatibility (CI). In CI, Wolbachia infection of males causes embryonic lethality unless they mate with similarly infected females, creating a relative reproductive advantage for infected females. A set of related Wolbachia bicistronic operons encodes the CI-inducing factors. The downstream gene encodes a deubiquitylase or nuclease and is responsible for CI induction by males, while the upstream product when expressed in females binds its sperm-introduced cognate partner and rescues viability. Both toxin-antidote and host-modification mechanisms have been proposed to explain CI. Interestingly, male killing by either Spiroplasma or Wolbachia endosymbionts involves deubiquitylases as well. Interference with the host ubiquitin system may therefore be a common theme among endosymbiont-mediated reproductive alterations.
An economic evaluation of Wolbachia deployments for dengue control in Vietnam
25418H. C. Turner, D. L. Quyen, R. Dias, P. T. Huong, C. P. Simmons and K. L. Anders, PLOS Neglected Tropical Diseases, 17:e0011356. 2023-05-30 07:56:11.
INTRODUCTION: Dengue is a major public health challenge and a growing problem due to climate change. The release of Aedes aegypti mosquitoes infected with the intracellular bacterium Wolbachia is a novel form of vector control against dengue. However, there remains a need to evaluate the benefits of such an intervention at a large scale. In this paper, we evaluate the potential economic impact and cost-effectiveness of scaled Wolbachia deployments as a form of dengue control in Vietnam-targeted at the highest burden urban areas. METHODS: Ten settings within Vietnam were identified as priority locations for potential future Wolbachia deployments (using a population replacement strategy). The effectiveness of Wolbachia deployments in reducing the incidence of symptomatic dengue cases was assumed to be 75%. We assumed that the intervention would maintain this effectiveness for at least 20 years (but tested this assumption in the sensitivity analysis). A cost-utility analysis and cost-benefit analysis were conducted. RESULTS: From the health sector perspective, the Wolbachia intervention was projected to cost US$420 per disability-adjusted life year (DALY) averted. From the societal perspective, the overall cost-effectiveness ratio was negative, i.e. the economic benefits outweighed the costs. These results are contingent on the long-term effectiveness of Wolbachia releases being sustained for 20 years. However, the intervention was still classed as cost-effective across the majority of the settings when assuming only 10 years of benefits. CONCLUSION: Overall, we found that targeting high burden cities with Wolbachia deployments would be a cost-effective intervention in Vietnam and generate notable broader benefits besides health gains.
The optimal strategy of incompatible insect technique (IIT) using Wolbachia and the application to malaria control
25203T. Matsufuji and S. Seirin-Lee, Journal of Theoretical Biology, 569:111519. 2023-05-29 09:18:33.
For decades, techniques to control vector population with low environmental impact have been widely explored in both field and theoretical studies. The incompatible insect technique (IIT) using Wolbachia, based on cytoplasmic incompatibility, is a technique that Wolbachia-infected male mosquitoes are incapable of producing viable offspring after mating with wild-type female mosquitoes. While the IIT method experimentally ensured its effectiveness in several field works, the failure of female mosquito population control by replacement owing to the accidental contamination of Wolbachia-infected female mosquitoes has been a concern and an obstacle in implementing the IIT method in nature. In this study, we develop a population-based IIT mathematical model using cytoplasmic incompatibility and evaluate the effectiveness of the IIT method in scenarios where contamination is present or absent. In addition, by extending the model to assess the disease infection status of the human population with malaria, we evaluate the optimal release strategy and cost for successful disease control. Our study proves that IIT could be a promising method to control mosquito-borne diseases without perfect suppression of vector mosquito population regardless of contamination.
The boundary problem: Defining and delineating the community in field trials with gene drive organisms
25098N. de Graeff, I. Pirson, R. van der Graaf, A. L. Bredenoord and K. R. Jongsma, Bioethics, 2023-05-03 10:11:03.
Despite widespread and worldwide efforts to eradicate vector-borne diseases such as malaria, these diseases continue to have an enormous negative impact on public health. For this reason, scientists are working on novel control strategies, such as gene drive technologies (GDTs). As GDT research advances, researchers are contemplating the potential next step of conducting field trials. An important point of discussion regarding these field trials relates to who should be informed, consulted, and involved in decision-making about their design and launch. It is generally argued that community members have a particularly strong claim to be engaged, and yet, disagreement and lack of clarity exist about how this "community" should be defined and delineated. In this paper, we shed light on this "boundary problem": the problem of determining how boundaries of inclusion and exclusion in (GDT) community engagement should be drawn. As our analysis demonstrates, the process of defining and delineating a community is itself normative. First, we explicate why it is important to define and delineate the community. Second, we demonstrate that different definitions of community are used and intermingled in the debate on GDTs, and argue in favor of distinguishing geographical, affected, cultural, and political communities. Finally, we propose initial guidance for deciding who should (not) be engaged in decision-making about GDT field trials, by arguing that the definition and delineation of the community should depend on the rationale for engagement and that the characteristics of the community itself can guide the effective design of community engagement strategies.
Targeting Sex Determination to Suppress Mosquito Populations
24988L. Ming, P. K. Nikolay, S. Ruichen, Y. Ting, D. B. Elena, J. B. Daniel, A. Igor, M. S. C. Hector, Z. Yinpeng, A. D. Nicolas, M. L. YuMin, P. S. Matthew, M. Craig, M. M. John and S. A. Omar, bioRxiv, 2023.04.18.537404. 2023-04-20 14:45:03.
Each year, hundreds of millions of people are infected with arboviruses such as dengue, yellow fever, chikungunya, and Zika, which are all primarily spread by the notorious mosquito Aedes aegypti. Traditional control measures have proven insufficient, necessitating innovations. In response, here we generate a next generation CRISPR-based precision-guided sterile insect technique (pgSIT) for Aedes aegypti that disrupts genes essential for sex determination and fertility, producing predominantly sterile males that can be deployed at any life stage. Using mathematical models and empirical testing, we demonstrate that released pgSIT males can effectively compete with, suppress, and eliminate caged mosquito populations. This versatile species-specific platform has the potential for field deployment to control wild populations, safely curtailing disease transmission.Competing Interest StatementO.S.A. is a founder of Agragene, Inc. with equity interest. O.S.A., M.L., and N.P.K are founders of Synvect with equity interest. The terms of this arrangement have been reviewed and approved by the University of California, San Diego in accordance with its conflict of interest policies. All remaining authors declare no competing interests.
First transgenic mosquito made in Africa by Transmission Zero
24962H. Dunning, Imperial College London, 2023-04-04 10:33:04.
Transmission Zero, a global scientific programme led by scientists at Imperial College London and the Ifakara Health Institute (IHI) of Tanzania, in partnership with the Tanzanian National Institute of Medical Research (NIMR), announces the generation of the first transgenic mosquito strain ever to be made in Africa.This strain carries in its genome genetic modifications that will allow scientists in the future to render mosquitoes unable to transmit malaria. This major scientific achievement is a pivotal milestone in the renewed international efforts to rid Africa of malaria. Half of the world’s population is at risk of contracting malaria, a disease caused by parasites that are transmitted from one person to another through mosquito bites. In 2021 alone, there were over 247 million cases and 619,000 deaths from malaria, mostly children under five years old in sub-Saharan Africa.
A gene drive is a gene drive: the debate over lumping or splitting definitions
24910S. L. James, D. A. O'Brochta, F. Randazzo and O. Akbari, Nature Communications, 2023-03-29 12:22:20.
Gene drive technologies are being considered as a new approach to address a variety of currently intractable global problems, including to prevent disease transmission, reduce crop loss, and preserve biodiversity1. There are some outside the genetics research community who argue that wide use of the term “gene drive” to encompass selfish genetic elements found either in extant organisms (natural gene drives) or assembled in the laboratory (synthetic gene drives) will discourage the necessary scrutiny of risks that may be associated with the introduction of synthetic gene drives into free-living populations of target organisms2,3. Here we argue that the current definition is both scientifically sound and promotes good governance.
Synthetic gene drives as an anthropogenic evolutionary force
24895A. D. Cutter, Trends in Genetics, 2023-03-28 07:24:22.
Genetic drive represents a fundamental evolutionary force that can exact profound change to the genetic composition of populations by biasing allele transmission. Herein I propose that the use of synthetic homing gene drives, the human-mediated analog of endogenous genetic drives, warrants the designation of ‘genetic welding’ as an anthropogenic evolutionary force. Conceptually, this distinction parallels that of artificial and natural selection. Genetic welding is capable of imposing complex and rapid heritable phenotypic change on entire populations, whether motivated by biodiversity conservation or public health. Unanticipated possible long-term evolutionary outcomes, however, demand further investigation and bioethical consideration. The emerging importance of genetic welding also compels our explicit recognition of genetic drive as an addition to the other four fundamental forces of evolution.

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