Perspectives
Opinions on and about gene drive technologies and their uses.
Gene Drives Could Fight Malaria and Other Global Killers but Might Have Unintended Consequences
24460M. Cobb, Scientific American, 2023-01-13 08:22:55.
Every year more than 600,000 people die from mosquito-transmitted malaria, most of them children under age five. Some insects that are disease vectors, such as mosquitoes, are currently expanding their range around the world, bringing new threats. Genetic engineering can fix this by permanently altering insect genes through what is known as a gene drive. This technology allows a chosen set of genes to alter an animal’s biology in some way, such as making them produce sterile offspring. The inability to reproduce then sweeps through a population, upending the laws of inheritance. The genes copy themselves exponentially from generation to generation, rapidly coming to dominate the whole population. Potentially, their careful use might save millions of lives by making mosquitoes unable to transmit malaria or by eliminating the insects entirely. The possibility of a definitive solution to major infectious diseases makes a compelling case for a such a techno fix.
CRISPR Gene Drives: A Weapon of Mass Destruction?
24336J. Ng, Medium, 2022-12-29 08:40:22.
Gene drives allow scientists to “drive” new genes — and their associated traits — into wildlife populations at unprecedented rates. Here’s a simplified explanation of how gene drives work. In normal sexual reproduction between species with two copies of chromosomes, each gene has a 50% chance of being inherited. However, there are particular DNA sequences called “selfish genes” whose frequency in the genome increases with each generation, even if this doesn’t result in an evolutionary advantage for the offspring. In 2003, biologist Austin Burt proposed a new way to use selfish genes to spread traits more efficiently through a population and ensure that offspring have a 100% probability of inheriting a particular DNA segment.
Genes drive organisms and slippery slopes
24322D. B. Resnik, R. F. Medina, F. Gould, G. Church and J. Kuzma, Pathog Glob Health, 2022-12-22 08:58:12.
The bioethical debate about using gene drives to alter or eradicate wild populations has focused mostly on issues concerning short-term risk assessment and management, governance and oversight, and public and community engagement, but has not examined big-picture- 'where is this going?'-questions in great depth. In other areas of bioethical controversy, big-picture questions often enter the public forum via slippery slope arguments. Given the incredible potential of gene drive organisms to alter the Earth's biota, it is somewhat surprising that slippery slope arguments have not played a more prominent role in ethical and policy debates about these emerging technologies. In this article, we examine a type of slippery slope argument against using gene drives to alter or suppress wild pest populations and consider whether it has a role to play in ethical and policy debates. Although we conclude that this argument does not provide compelling reasons for banning the use of gene drives in wild pest populations, we believe that it still has value as a morally instructive cautionary narrative that can motivate scientists, ethicists, and members of the public to think more clearly about appropriate vs. inappropriate uses of gene drive technologies, the long-term and cumulative and emergent risks of using gene drives in wild populations, and steps that can be taken to manage these risks, such as protecting wilderness areas where people can enjoy life forms that have not been genetically engineered.
Gene drive-mediated population elimination for biodiversity conservation. When you come to a fork in the road, take it
24281B. A. Hay and M. Guo, Proceedings of the National Academy of Sciences, 119:e2218020119. 2022-12-20 14:19:44.
How can the ability of t w2 to spread at super-Mendelian frequencies be utilized even if it is unable to directly drive the population to an unfit state? Gierus, Birand, and colleagues proposed placing Cas9 and a gRNA at a neutral position within the t haplotype. In this hybrid gene drive element, which they refer to as tCRISPR, Cas9 and the gRNA cleave and (hopefully) create loss-of-function (LOF) alleles in the male germ line of the prolactin (Prl) gene, which is required for female fertility. The goal with tCRISPR is for t-based segregation distortion in males to pump the Cas9/gRNAs cassette to high frequency within the population. The latter, through cleavage followed by inaccurate repair in males, will continuously produce LOF alleles at the independently segregating Prl locus. The hope is that the combination of t-based drive and accumulation of Prl LOF alleles will drive the population to an unfit state that contains a high frequency of infertile homozygous Prl mutant females along with some frequency of infertile homozygous t males. The combination of these two effects, they propose, could eliminate populations under a wider range of parameters than with t w2 alone
Gene editing and agrifood systems
24291FAO, FAO, 2022-12-20 09:22:56.
Gene-editing technologies represent a promising new tool for plant and animal breeding in low- and middle-income countries. They enhance precision and efficiency over current breeding methods and could lead to rapid development of improved plant varieties and animal breeds. However, as for any new technology, they have their merits and demerits. There is, as yet, no international consensus regarding if and how gene-edited organisms should be regulated, and whether their release would fall under the regulatory framework of the Cartagena Protocol on Biosafety to the Convention on Biological Diversity. This science- and evidence-based Issue Paper on gene editing and agrifood systems presents a balanced discussion of the most pertinent aspects of gene editing, including the consequences for human hunger, human health, food safety, effects on the environment, animal welfare, socioeconomic impact and distribution of benefits. Intrinsic ethical concerns and issues of governance and regulation are addressed, and the roles of the public and private sectors, alone and in partnership, are summarized. Various scenarios are also presented for how gene editing might be used in the future to help transform agrifood systems.
Exploring the value of a global gene drive project registry
24279R. I. Taitingfong, C. Triplett, V. N. Vásquez, R. M. Rajagopalan, R. Raban, A. Roberts, G. Terradas, B. Baumgartner, C. Emerson, F. Gould, F. Okumu, C. E. Schairer, H. C. Bossin, L. Buchman, K. J. Campbell, A. Clark, J. Delborne, K. Esvelt, J. Fisher, R., Nature Biotechnology, 2022-12-15 14:15:40.
Recent calls to establish a global project registry before releasing any gene-drive-modified organisms (GDOs) have suggested a registry could be valuable to coordinate research, collect data to monitor and evaluate potential ecological impacts, and facilitate transparent communication with community stakeholders and the general public. Here, we report the results of a multidisciplinary expert workshop on GDO registries convened on 8–9 December 2020 involving 70 participants from 14 countries. Participants had expertise in gene drive design, conservation and population modeling, social science, stakeholder engagement, governance and regulation, international policy, and vector control; they represented 45 organizations, spanning national and local governmental agencies, international organizations, nonprofit organizations, universities, and district offices overseeing local vector control. The workshop aimed to gather perspectives on a central question: “In what ways could a gene-drive project registry both contribute to and detract from the fair development, testing and use of GDOs?” We specifically queried the perceived purpose of a registry, the information that would need to be included, and the perceived value of a registry. Three primary findings emerged from the discussion: first, many participants agreed a registry could serve a coordinating function for multidisciplinary and multisector work activities; second, doing so may require different design elements, depending on the target end-user group and intended purpose for that group; and third, these different information requirements lead to concerns about information sharing via a registry, suggesting potential obstacles to achieving transparency through such a mechanism. We conclude that any development of a gene-drive project registry requires careful and inclusive deliberation, including with potential end-users, to ensure that registry design is optimal.
Good news in the fight against vector-borne diseases
24175K. Magori, 2022-12-09 11:07:13.
At the turn of the century, several research groups attempted to apply modern genetic methodologies to achieve similar outcomes without the need for irradiation and the resulting fitness costs. Luke Alphey and his colleagues at Oxford University developed a dominant lethal genetic system for autocidal control in the Mediterranean fruitfly, where a transactivator causes lethality in the early developmental stages of heterozygous insects unless repressed by tetracycline. The company he funded (Oxitec Limited) successfully adapted this system in several agriculturally important pest species, as well as in Aedes aegypti and other mosquitoes. (Full disclosure: I worked at Oxitec Limited in 2007, but own no shares or have any other conflict of interest with them). While the first generation of these mosquitoes proved to successfully reduce wild-type mosquito populations, they required labor-intensive separation of male and female mosquitoes before release in close proximity. While this ensured that only non-biting male mosquitoes are released, it also limited the scalability of this approach.
No Environmental Release of Gene Drive Organisms
24114Anonymous, STOP GENE DRIVES, 2022-11-30 09:32:55.
We urge governments to prevent the environmental release of gene drive organisms and to establish a global moratorium on the release of gene drive organisms at the UN Convention on Biological Diversity (CBD). Gene drives work against natural rules of inheritance forcing nearly 100% instead of the usual 50% of offspring to inherit their genetically engineered traits. Whereas existing biosafety systems are designed to limit the spread and persistence of living modified organisms to mitigate against adverse impacts, gene drives are intended to spread genetic modifications to alter species and ecosystems. This would undermine the integrity of the UN Cartagena Protocol and international and national biosafety systems, including the procedures for Advanced Informed Agreement (AIA) of countries and Free, Prior and Informed consent (FPIC) of Indigenous Peoples and local communities.
Should we use a genetic weapon against mosquitoes carrying malaria?
23988T. H. Saey, ScienceNewsExplores, 2022-11-17 08:58:08.
In a large laboratory cage, a male mosquito carries a genetic weapon that could launch the destruction of his species. That loss could also mean the end of the parasite that causes malaria. The weapon? A self-replicating bit of DNA known as a gene drive. It’s one of the most anticipated tools being developed to stop mosquitoes from spreading diseases like malaria to humans. It’s also one of the most controversial. The gene drive interferes with the insects’ ability to reproduce. In one small lab study, it wiped out captive populations of mosquitoes in just eight to 12 generations. A larger study in outdoor cages in Terni, Italy, worked too. Within as little as five to 10 years, this gene drive could be ready to test in the wild. Researchers are eyeing Africa for the first test release. There, malaria takes a huge toll. In 2020, it sickened close to 241 million people on the continent. And most of the globe’s 670,000 malaria deaths that year were in Africa. About eight in every 10 were children, the World Health Organization says. Many tools have been made to fight the disease. There are preventive drugs, insecticide-treated bed nets and even vaccines. These efforts are helping. But mosquitoes are developing resistance to insecticides. And some anti-malaria drugs may no longer work well. “To go toward zero [cases], we need to have something that is transformational,” says Fredros Okumu. By that, he means a completely new type of strategy. Okumu is a mosquito biologist. He directs science programs at Ifakara Health Institute in Tanzania, a country in East Africa. Gene drives might be the big change people are looking for. This technology was first devised in 2015. Researchers are still refining and testing it. Other types of genetically altered mosquitoes have been released in Brazil, the United States and elsewhere. But so far, those altered genes spread slowly among wild populations. Gene drives could potentially spread to nearly every member of a species quickly. In this way, they could forever alter the species. Or even wipe it out.
Driving lessons: a brief (personal) history of centromere drive
24030H. S. Malik, Genetics, 2022-11-15 09:41:41.
Meiosis is an important specialized cell division in many eukaryotic species, including fungi, plants, and animals. Meiosis results in the production of haploid gametes starting from a diploid cell via 1 round of replication and 2 rounds of cell division. In an influential article published in 1957, Sandler and Novitski first pointed out that meiosis is also an intense battleground, in which gametes vie for evolutionary supremacy with each other, often poisoning their competition to gain a fratricidal advantage (Sandler and Novitski 1957). This competition, which they termed “meiotic drive,” operates as an evolutionary force that can cause an increase in frequency of the allele that is favored during meiotic transmission. Unlike alleles that rise in frequency because they confer a fitness advantage to their carriers, meiotic drivers can rise in frequency even while conferring significant fitness disadvantages on their carriers. Thus, meiotic drivers can be viewed as the quintessential selfish genes; it is the best interest of the rest of the genome to counteract their action to restore organismal fitness.
SHOULD WE CREATE GENE DRIVE GREY SQUIRRELS
23962S. Hartley and T. Law, GeneDriveGovernance.org, 2022-11-09 11:48:04.
UK scientists have proposed gene drive as a management tool to control grey squirrels. Now is a good time to talk about this emerging technology because the hopes and concerns of experts, stakeholders and the public can help to determine if or how it might be developed. To help foster this debate, we made a short research film on gene drive grey squirrels. The film draws on our social science research to show the complexity of the problem of grey squirrel control and invites you to think about whether scientists should develop gene drive squirrels or not.
WORLDWIDE: EXPERTS ON GENE DRIVES
23840Stop Gene Drive, STOP GENE DRIVES, 2022-11-07 09:51:54.
We are travelling the world speaking to some of the world’s leading thinkers, activists and academics on the impact of gene drives. We interviewed more than 20 experts from around the world
Externalities modulate the effectiveness of the Wolbachia release programme
23611E. E. Ooi and A. Wilder-Smith, The Lancet Infectious Diseases, 2022-09-28 09:16:47.
Despite the remarkable outcome in Yogyakarta, the wMel approach also has some challenges. In particular, the extent to which ecological, weather, and other external factors influence the dissemination and establishment of wMel in complex urban environments remains unclear. Whether the high and sustained penetration rate of wMel and the efficacy in preventing dengue that was observed in Yogyakarta are readily reproducible in other regions of the world that are vulnerable to repeated outbreaks of such viral diseases is also unclear. We therefore welcome the study into the real-world effectiveness of large-scale wMel release in the urban setting of Rio de Janeiro.3 The study assessed the rate of wMel introgression at the neighbourhood level and its effect on the localised incidence of dengue and chikungunya. Mosquitoes were released over a 2·5-year period starting in August, 2017.
Extreme GM “extinction technology” of gene drives presented as “natural”
23625GM Watch, GM Watch, 2022-09-19 14:45:48.
Now similar Orwellian moves are happening in the area of gene drives. A gene drive is a genetic engineering technology that forces a particular genetic modification through a population by changing the natural rules of inheritance, usually to ensure that it is increasingly – or always – inherited. Gene drive organisms are built to intentionally spread their engineered traits through an entire population, turning on its head the usual imperative to try to contain and prevent engineered genes from contaminating and disrupting ecosystems. They can be designed to re-model or delete entire species. Gene drive technology is deeply unpopular and rightly feared by the public and regulators. It is against this background that in recent years, some researchers have begun to describe so-called "selfish genetic elements" found in nature* as "natural gene drives" and to present gene drive as a "ubiquitous natural phenomenon".
Humans Have a Long History of Making ‘Very Bad Decisions’ to Save Animals
23627T. McDonnell, The New York Times, 2022-09-17 07:17:21.
Environmental reporter Tim McDonnell on the potential negative consequences of animal conservation efforts. McDonnell highlights Target Malaria’s research on gene drive to “eliminate malaria-carrying mosquitos” and quotes New Zealand researcher Philipp Messer saying that the world is “ill-prepared” for a "real-life gene drive.” The article also quotes MIT biologist Kevin Esvelt saying that misuse of the technology would cause the public and policymakers to halt gene drive research and would set the field back by a decade. The article notes that there is no international regulation to “prevent the premature deployment of gene drive in the wild” and states that “individual governments, powerful funding organizations like the Bill and Melinda Gates Foundation, and scientists themselves” are responsible for balancing the prevention of risky interventions with the need to support basic research. Esvlet is also quoted saying that the WHO needs to “establish a registry for all gene drive experiments that requires scientists to detail safeguards and find a local community who agrees to guide the research before experiments begin.”
Toward product-based regulation of crops
23498F. Gould, R. M. Amasino, D. Brossard, C. R. Buell, R. A. Dixon, J. B. Falck-Zepeda, M. A. Gallo, K. E. Giller, L. L. Glenna, T. Griffin, D. Magraw, C. Mallory-Smith, K. V. Pixley, E. P. Ransom, D. M. Stelly and C. N. Stewart, Science, 377:1051-1053. 2022-09-02 19:04:01.
Current process-based approaches to regulation are no longer fit for purpose Much effort has been expended globally over the past four decades to craft and update country-specific and multinational safety regulations that can be applied to crops developed by genetic engineering processes, while exempting conventionally bred crops. This differentiation made some sense in the 1980s, but in light of technological advances, it is no longer scientifically defensible. In the coming decades, innovations in genetic engineering and modern ?conventional? processes of crop development will enable use of these approaches to alter more crops and more traits. Future governance of new plant varieties and foods, regardless of the processes and techniques used to develop them, will require new, scientifically sound assessment methodologies, developed in a manner acceptable to society. Here, we provide a rationale for one governance approach that moves away from current process-based regulation and uses newly developed molecular techniques that enable detailed characterization of the new crops and foods themselves.
Outbreaks of arboviruses, biotechnological innovations and vector control: facing the unexpected
23438C. Boëte, Innovative Strategies for Vector Control, 6:219-231. 2022-08-19 09:19:15.
Outbreaks of arboviruses have occurred in the last decades in many places around the world and a variety of responses have been taken in order to control them. Responses ranged from vaccination campaigns to the use of conventional vector control methods. Innovative approaches relying on biotechnological novelties, often still under development, have been considered despite the lack of solid evidence of their efficacy. While discussing these different aspects of the fight against vector-borne diseases with a focus on the context of outbreaks, this chapter considers the social and ethical aspects related to both the rhetoric and the discussion about the implementation of new and innovative approaches.
Natural selfish genetic elements should not be defined as gene drives
23435M. A. Wells and R. A. Steinbrecher, Proceedings of the National Academy of Sciences, 119:e2201142119. 2022-08-16 07:53:39.
Gene drives are increasingly discussed in the political realm,and how the term is defined therefore has important impli-cations. The opinion piece from Alphey et al. (1) identifies alack of consensus on the definition and makes explicitchanges in how the terminology is being used by someresearchers. As such it is a timely invitation for debate.The definition of the term“gene drive”Alphey et al. (1)propose would include naturally occurring selfish geneticelements (SGEs) and natural processes causing biasedinheritance. We disagree with this aspect of the proposal,which does not reflect the original use of the term, whichrelated to engineered system
What can we learn from selfish loci that break Mendel’s law?
23349S. E. Zanders, PLOS Biology, 20:e3001700. 2022-07-19 07:31:24.
Mendel’s law of segregation provides a critical foundation for genetic inquiry It is not, however, without exceptions Historically, 2 such exceptions (sex chromosome linkage and chromosome missegregation in meiosis) were used by Drosophila geneticists to help demonstrate that genes are carried on chromosomes Looking forward, modern geneticists interested in understanding the mechanisms of heredity have much to learn from additional exceptions to Mendel’s law In particular, selfish genes that break Mendel’s law of segregation to gain a transmission advantage into the next generation are likely to be oversized contributors to shaping the process of sexual reproduction These selfish genes exploit reproduction such that a given selfish locus is transmitted to more than half of the offspring produced by an organism There are a variety of selfish DNAs, but here I will focus on transposable elements and drive loci as examples Transposable elements can generate novel copies of themselves using copy and paste or cut and paste mechanisms Importantly, transposable elements are selected to mobilize in the germline as that allows new copies to be passed on to subsequent generations Drive loci preferentially bias their own transmission such that a driver+ /driver− heterozygote will pass the driver+ allele to more than half of its viable progeny Drivers are diverse and can act during meiosis, gametogenesis, or post-fertilization Both transposable elements and drivers are found throughout eukaryotes, including humans
Mendel’s laws of heredity on his 200th birthday: What have we learned by considering exceptions?
23269J. B. Wolf, A. C. Ferguson-Smith and A. Lorenz, Heredity, 129:1-3. 2022-07-01 07:36:08.
Violations of Mendel’s laws can generically be referred to as ‘non-Mendelian inheritance’. However, from that broad perspective, nearly all inheritance systems would show non-Mendelian inheritance (at least to some degree). To hold exactly, Mendel’s laws impose strict requirements: a locus has to contain two allelic variants that have discrete effects on categorical (or at least discrete and countable) traits, and they must show complete dominance. These strict conditions are rarely met in real systems (Hou et al. 2016), both because allelic effects do not adhere to the strict law of dominance and because many traits of interest show continuous variation. Mendel recognised many of the exceptions related to effects of alleles, such as the presence of incomplete dominance, pleiotropy, and epistasis (see Fairbanks 2022, this volume), and Fisher (1918) reconciled the assumption of Mendelian inheritance with continuous variation. Hence, from this perspective, a large array of scenarios that show nonMendelian inheritance are actually consistent with the conceptual foundation of Mendel’s perspective based on elemental inheritance
Contact Us
Alex Sullivan
Foundation for the
National Institutes of Health
geneconvenevi@fnih.org