Perspectives
Opinions on and about gene drive technologies and their uses.
Gene drive in plants emerges from infancy
28152M. J. A. Awan, R. Z. Naqvi, I. Amin and S. Mansoor, Trends in Plant Science, 2023-10-18 11:43:35.
Selfish genetic elements (SGEs) display biased transmission to offspring. However, their breeding potential has remained obscure. Wang et al. recently reported a natural gene-drive system that can be harnessed to prevent hybrid incompatibility and to develop a synthetic gene-drive (SGD) system for crop improvement.
The double-edged sword effect of expanding Wolbachia deployment in dengue endemic settings
28137M. G. Pavan, G. A. Garcia, M. R. David and R. Maciel-de-Freitas, The Lancet Regional Health - Americas, 27:100610. 2023-10-02 10:16:37.
We can use Brazil as a showcase to foresee and avoid a double-edged sword effect associated with Wolbachia releases. Insecticide resistance of native Ae. aegypti populations is spread worldwide (http://aedes.irmapper.com), and positive results should boost Wolbachia deployment in other dengue endemic settings around the world. Aedes aegypti populations are heterogeneous and nationwide releases of a Wolbachia strain whose genetic backcross belong to a specific locality would produce an unsought homogenization of vector populations. Aedes aegypti homogenisation at large geographic scales could impose additional undesirable consequences in the long-term by promoting genetic hitchhiking of traits such as higher vector competence, lower susceptibility to repellents and insecticides, or more avid host-seeking and biting behaviour. Available data has shown that ensuring adherence to local characteristics, specially a matching genetic between native and released mosquitoes, is critical to enhance the likelihood of achieving a faster introgression in the field, realizing cost and time savings over the globe. Probably there are a myriad of yet undiscovered traits beyond insecticide resistance that may influence vector local adaptation and would affect the success of released strains. Therefore, neglecting the genetic diversity in favour of centralising the rearing of mosquitoes with Wolbachia for nationwide releases could represent a drawback for future releases. Long-term studies regarding the consequences of releasing mosquitoes with homogenous genotypes in diverse ecological and epidemiological scenarios remain a critical research priority, essential for informed decision-making and sustainable management of mosquito-borne diseases.
Engineered and natural gene drives: mechanistically the same, yet not same in kind
27995R. F. Medina and J. Kuzma, Nature Communications, 14:5994. 2023-09-26 08:18:08.
We propose the use of the terms natural gene drive (NGD) and engineered gene drive (EGD) arguing against James et al.1, who think both should be included within the term “gene drive”, based on their mechanistic similarities. Thanks to CRISPR-Cas-based gene editing, engineered gene drive has suddenly become feasible as a potential cost-effective pest control tool that could help us resolve wicked challenges2,3 . In nature, several organisms harbor genes that “selfishly” drive themselves into populations. This natural gene drive uses similar mechanisms to the ones use today to drive engineered genes into laboratory populations4 article we disagree with James et al.1 .In this who have recently proposed that because natural and engineered gene drives are mechanistically indistinguishable from a molecular standpoint, they should both be referred as “gene drives” because “a gene drive is a gene drive.” We instead propose that two terms be used to distinguish between natural and engineered gene drives, we second Wells and Steinbrecher5 arguments, and propose to use the terms natural gene drive (NGD) and engineered gene drive (EGD).
Unleashing the swarm: Battling the global mosquito menace and defending public health
26467J. Entine and S. Moxon, Genetic Literacy Project, 2023-07-05 07:47:22.
There is one solution embraced by global health experts that should be pursued aggressively, if with some caution. Scientists in real-world trials have altered the genomes of entire animal populations, including mosquitoes, to thwart the vectoring of diseases and control pests — an innovation called gene drives. Emerging gene drive technologies offer enormous potential and have already shown their value in test projects in many parts of the world. More recently, the application of CRISPR/Cas9 tools has dramatically accelerated their effectiveness. But implementation on a wider scale is progressing at a snail’s pace. Why? For the most part, it is restrained by controversy, misunderstanding and the political opposition of activist environmental groups in Europe and North America.
Gene Drive technologies for Malaria control in Africa: Who Should call the shots?
2023-07-05 06:08:24.Guerrilla eugenics: gene drives in heritable human genome editing
26475A. D. Cutter, J Med Ethics, 2023-07-04 08:15:56.
CRISPR-Cas9 genome editing can and has altered human genomes, bringing bioethical debates about this capability to the forefront of philosophical and policy considerations. Here, I consider the underexplored implications of CRISPR-Cas9 gene drives for heritable human genome editing. Modification gene drives applied to heritable human genome editing would introduce a novel form of involuntary eugenic practice that I term guerrilla eugenics. Once introduced into a genome, stealth genetic editing by a gene drive genetic element would occur each subsequent generation irrespective of whether reproductive partners consent to it and irrespective of whether the genetic change confers any benefit. By overriding the ability to 'opt in' to genome editing, gene drives compromise the autonomy of carrier individuals and their reproductive partners to choose to use or avoid genome editing and impose additional burdens on those who hope to 'opt out' of further genome editing. High incidence of an initially rare gene drive in small human communities could occur within 200 years, with evolutionary fixation globally in a timeframe that is thousands of times sooner than achievable by non-drive germline editing. Following any introduction of heritable gene drives into human genomes, practices intended for surveillance or reversal also create fundamental ethical problems. Current policy guidelines do not comment explicitly on gene drives in humans. These considerations motivate an explicit moratorium as being warranted on gene drive development in heritable human genome editing.
Malaria Cases In U.S. Trigger Unfounded Claims About Bill Gates, Mosquito Project
26378B. Y. Lee, Forbes, 2023-07-01 07:03:59.
When the U.S. Centers for Disease Control and Prevention (CDC) issued an alert about finding four malaria cases in Florida and one malaria case in Texas, it created quite a buzz. After all, these were the first reported cases of people actually catching malaria in the U.S. since 2003. Finding these five cases has raised questions about whether malaria may return to the U.S. after being largely absent for many years and whether climate change may be opening the gates for Anopheles mosquitoes to spread in the U.S. That would kind of suck since the females of certain Anopheles mosquito species can carry and transmit malaria-causing parasites. This news also opened the gates in another way—allowing a flood of even more conspiracy theories about billionaire philanthropist Bill Gates to be spread across social media. This included claims that Gates was somehow responsible for these new malaria cases via a project that has released genetically-modified mosquitoes in the U.S. However, such claims really provided zzzzzero supporting evidence and, in fact, detracted from what’s really happened.
Worldwide Experts on Gene Drives
Save Our Seeds, 2023-06-28 08:54:11.We are travelling the world speaking to some of the world's leading thinkers, activists and academics on the impact of gene drives. Join us for this video series as we hear from a diverse range of experts on one of the most controversial new emerging technologies that we face.
Generation game: gene-edited mosquitos to fight malaria
25551J. Opara, Sci Dev Net, 2023-06-07 08:44:49.
Population-level changes in the genetic make-up of one of the world’s deadliest animals could provide a key in the fight against malaria, proponents of a radical new technology argue. So-called gene drive technology, where genetic changes are passed down through generations, could rein in mosquito populations, or prevent them from passing on malaria.“Through genetic engineering, researchers have modified mosquitoes to favour the inheritance of genes that either will reduce the size of the population of those mosquitoes or stop them from transmitting the malaria parasite,” Michael Santos, senior vice-president and chief population health sciences officer at the US-based charity the Foundation for the National Institutes of Health (FNIH), tells SciDev.Net. “In other words, [it is about] using mosquitoes to control mosquitoes.” Malaria is one of the world’s “big three” deadly diseases, killing over half a million people in 2021, the vast majority in Africa.
Cell biology: Selfish B chromosomes unleashed by a dysfunctional chromosome segregation system
25563P. Ferree, Current Biology, 33:R431-R434. 2023-06-05 09:18:59.
A study in the fruit fly Drosophila melanogaster shows that a defective chromosome segregation system allows non-essential B chromosomes to transmit at higher-than-Mendelian frequencies.
Genetically Engineered Mosquito experiment in California’s Central Valley halted
25147H. Bourque, Friends of the Earth, 2023-05-12 14:52:46.
In a victory for environmentalists, scientists and vulnerable agricultural communities across California, the California Department of Pesticide Regulation (DPR) announced yesterday the withdrawal of a permit request for a mass release of experimental genetically engineered mosquitoes in the Central Valley. The withdrawal of the biotech corporation Oxitec’s request halts the controversial proposed release of billions of genetically engineered insects. Scientists and other experts in the field have raised concerns about Oxitec’s proposal to release genetically engineered mosquitoes due to inadequate scientific review and lack of appropriate and relevant regulations, pressuring the company to disclose data critical to assessing potential public health and environmental impacts.
Editorial: Genetic control of insect pest species—achievements, challenges, and perspectives
25423I. Häcker, D. Bartsch, A. Choo and F. Marec, Frontiers in Bioengineering and Biotechnology, 11. 2023-05-05 08:12:07.
Genetic control is a type ofbiological control and a promising approach to regulate insect pest populations in a species-specific manner. It is based on targeting the reproductive capacity of the target pest species to reduce population size to non-critical levels. The best known and also very successful genetic control strategy is the Sterile Insect Technique (SIT), which entails the continuous mass-release ofirradiation-sterilized males ofa given species to produce infertile matings in the field, leading to the decline in the target population over time. To date, SIT is only available for a few species, as its transfer to new target species is challenging and time consuming. Key aspects of this classical SIT and challenges in applying it to new pest species include mass rearing of target species, mass removal of female insects prior to irradiation and release, the sterilization procedure, and the biological quality control of the sterile insects produced. Besides this classical SIT strategy, current research efforts are also focused on the development of genetic control approaches based on transgenic, symbiont-mediated, or gene-drive strategies. Modern genetic technologies offer new solutions for the improvement of existing genetic control strategies and insect strains, for faster and easier transfer of existing strategies to new target species, and also for the development of new genetic control approaches. Publications within this Research Topic address pressing questions and challenges related to the genetic control of insect pests.
Probing “Selfish” Centromeres Unveils an Evolutionary Arms Race
24935M. Lampson, The Scientist, 2023-04-03 10:08:47.
The so-called Robertsonian (Rb) fusions that led to these rapid karyotype changes are relatively common chromosomal rearrangements. But their accumulation in the populations of Madeira Island and in multiple other isolated mouse populations elsewhere is likely due to another influencing factor: the preferential segregation of the Rb fusion into the egg rather than into the discarded polar bodies that form during female meiosis. We usually think of the chromosome segregation machinery as ensuring unbiased, random segregation. As we learn in high school biology, if a diploid individual carries two different alleles of a gene (i.e., is heterozygous), then either allele is equally likely to end up in a haploid gamete. This law explains the 3:1 ratio of phenotypes that Mendel observed in his classic studies of heredity. Scientists have known for decades, however, that selfish genes can subvert Mendelian segregation to increase their frequency in the next generation, a phenomenon known as meiotic drive. The Madeira mice suggest that fusion chromosomes can also drive unequal inheritance.
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.
Gene Drives Are Coming
24887D. Lowe, Science, 2023-03-23 08:26:31.
Consider the “gene drive” idea - there are a lot of variations, but the general idea is that you introduce a genetic sequence into an organism that can bias (drive) its own inheritance into the next generation. This is a thumb-on-the-scale unnatural selection if ever there was one, because that biased inheritance is outside of any fitness advantage that the new sequence might bring with it. In fact, a number of gene drive ideas have the opposite sign, conferring catastrophic unfitness in order to wipe out pathogens and disease-vector organisms.Gene drives of various kinds show up in nature, though, when a gene has some sort of ability to control its own transmission. These are the so-called “selfish genes”, and some of these have no fitness advantage (or even some disadvantage) in the organisms themselves. There are a lot of potential mechanisms for this (see that link for a good review), but what you don’t see are the total-wipeout forms just mentioned, which is what we has humans might like to do to (say) mosquitos or tsetse flies. The advent of CRISPR-Cas9 technology has really brought a lot more attention to these ideas, because they make them far more possible, for better or worse.
Gene Drives: Target Malaria is underestimating the risks
24867C. Then, Testbiotech, 2023-03-17 07:55:56.
The Target Malaria consortium has for several years been planning to conduct field trials using genetically engineered mosquitoes in Burkina Faso. The aim is to transfer artificial gene constructs, i. e. the so-called ‘X-shredder’, into wild populations of the mosquitoes. This gene construct is meant to reduce the number of female offspring, and thus bring about a decline in the overall population of mosquitoes (Anopheles gambiae) known to transmit malaria. However, as recent research shows, the planned releases are based on flawed data and incorrect assumptions.
Gene Drives and Vector-Borne Diseases: A Comparative Perspective Using Malaria as a Case Study
24818S. Todi, The Takshashila Institution, 2023-03-07 15:51:15.
Gene drives are an emerging technological application to reduce the prevalence of vector-borne diseases, crop pests, and non-native invasive species. This method for vector control is currently at the research stage, with parallel community engagement programmes being carried out in African countries to raise awareness for its adoption. Yet, the risks associated with using gene drives may go beyond the communities they are deployed in. Hence, it is critical for India to understand the relevance of gene drive application in India and its neighboring countries to create effective policy measures for achieving control of vector-borne diseases. Using malaria as a case study, we argue that India currently does not require the use of gene drives to achieve control of mosquito-borne diseases. However, India should invest in research for gene drives and vaccines, while continuing with current efforts to curb vector-borne diseases. Further, India will need strong data monitoring systems to identify if any gene drive mosquitoes deployed by other countries make their way to India.
Social justice environmental activists move to block gene editing to control invasive species and promote biodiversity. Here’s why they’re misguided
24701S. Smyth, Genetic Literacy Project, 2023-02-07 12:46:02.
Control of invasive species has been extremely difficult with eradication virtually impossible. To control invasive plant species, chemicals are commonly used while in some instances removal of plants by hand, as Shiva advocates, is undertaken. Efforts to control invasive animals include poisoning and shooting. Needless to say, these ‘control techniques’ are inefficient and often harmful to the applicators. Advances in genetics potentially offer new solutions, using gene editing technology to create sterile populations. Sterility is a natural trait in mammals, which can be induced into invasive animals as a means of population control. Invasive pests can be captured, gene-edited to confer sterility in future generations and then released back into the wild. The offspring will gradually without the use of chemicals or hand labor contribute to reduced populations. Applying gene editing technologies is not an instantaneous solution, but they may be part of a long-term strategy.
Complicated expansion trajectories of insertion sequences and potential association with horizontal transfer of Wolbachia DNA
24573Y. H. Miao, D. W. Huang and J. H. Xiao, Zoological Research, 44:273-275. 2023-01-22 08:41:24.
Insertion sequences (ISs) are the simplest structural transposable elements (TEs) in prokaryotes, consisting only of a transposase coding sequence and its bilateral short terminal inverted repeats. Due to their gradually streamlined genomic construction, TEs rarely exist in the genomes of obligate endosymbionts. However, TE content, especially ISs, is abundant in the genome of Wolbachia bacteria, obligate endosymbionts widespread in arthropods and nematodes. Although IS indels are reported to affect genome structure and gene function in Wolbachia, the distribution patterns, sources, and transfer trajectories of ISs remain poorly understood. Furthermore, whether IS transposition is associated with dynamic horizontal transfer of Wolbachia DNA is still unclear. Based on distribution patterns in supergroup A Wolbachia strains, ISs accounted for 11% of the genome of the Wolbachia strain wWpum, one of the highest IS genome coverages reported for Wolbachia to date. Three types of ISs showed rapid expansion in wWpum, possibly due to horizontal transfer from other Wolbachia strain supergroups or more distant prokaryotes. We also found the first evidence that ISs can carry flanking Wolbachia sequences for transposition, resulting in the horizontal transfer of Wolbachia DNA into the eukaryotic genome, thus implying a potential association between ISs and horizontal gene transfer from endosymbionts to eukaryotes.
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