Perspectives

Opinions on and about gene drive technologies and their uses.

Conservation demands safe gene drive

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K. M. Esvelt and N. J. Gemmell,  PLOS Biology,  15:e2003850. 2017-11-16 14:03:39.
Here, we explore the risk of accidental spread posed by self-propagating gene drive technologies, highlight new gene drive designs that might achieve better outcomes, and explain why we need open and international discussions concerning a technology that could have global ramifications.

Using CRISPR-based gene drive for agriculture pest control

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V. Courtier-Orgogozo, B. Morizot and C. Boëte,  EMBO Reports,  18:1481. 2017-09-01 13:15:07.
The authors respond to comments to their publication 10.15252/embr.201744205

Agricultural pest control with CRISPR-based gene drive: time for public debate

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V. Courtier-Orgogozo, B. Morizot and C. Boëte,  EMBO Reports,  18:878-880. 2017-06-01 14:19:16.
Gene drive technology to control disease vectors or pests has great potential for addressing humanitarian and public health problems. Its application for pest control in agriculture, however, raises important environmental, social and ethical issues.

National Academies hit the brakes on gene drive-modified organisms

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Abbasi, J.,  JAMA-Journal of the American Medical Association,  316:482-483. 2016-12-17 18:11:25.
Despite their potential for fighting Zika, malaria, and other public health scourges, organisms that have been engineered to quickly spread genetic modifications through a population—and possibly an entire species—are not ready for release into the wild, a committee of interdisciplinary experts concluded in a recent report by the National Academies of Sciences, Engineering, and Medicine (http://bit.ly/1UHuqQk). So-called gene drive–modified organisms “require more research in laboratories and highly controlled field trials,” the committee said in a statement (http://bit.ly/1tkWCTO). Gene drives are systems of “biased inheritance” that enhance a genetic element’s ability to pass from parent organism to offspring through sexual reproduction. These selfish genetic elements could be genes or their fragments, all or parts of chromosomes, or noncoding DNA, the report stated.

Gene Drives on the Horizon: Advancing Science, Navigating Uncertainty, and Aligning Research with Public Values

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U. S. National Academies of Sciences, Engineering, and Medicine,  The National Academies Press,  2016-07-08 20:32:51.
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. Just prior to the beginning of this study and since the committee was first convened, scientists published four proofs of concept— one in yeast, one in fruit flies, and two in different species of mosquitoes—that demonstrate the successful development of gene drives in the laboratory, at least in these organisms. Proposed applications for gene-drive modified organisms for basic research, conservation, agriculture, public health and other purposes will likely continue to expand as gene editing tools become more refined. Gene-drive modified organisms are on the horizon. The fast moving nature of this field is both encouraging and concerning. While gene-drive modified organisms hold promise for addressing difficult to solve, persistent challenges, such as the eradication of vector-borne diseases and the conservation of threatened and endangered species, these proposed applications are based on limited proof-of-concept studies. The presumed efficiency of gene-drive modified organisms may lead to calls for their release in perceived crisis situations, before there is adequate knowledge of their ecological effects, and before mitigation plans for unintended harmful consequences are in place. Responding to this fast moving field, the National Institutes of Health (NIH) and the Foundation for the National Institutes of Health (FNIH)2 asked the National Academies of Sciences, Engineering, and Medicine to convene a committee with a broad range of expertise to summarize the scientific discoveries related to gene drives and considerations for their responsible use. Proof-of-concept in a few laboratory studies is not sufficient in and of itself to support a decision to release gene-drive modified organisms into the environment. Laboratory and field research is needed to refine CRISPR/Cas9-based gene drives and other gene drive mechanisms, and to understand how gene drives might work under different environmental conditions and in a wide variety of organisms. The considerable gaps in knowledge about potential off-target (within the organism) and non-target (in other species or the environment) effects necessitate a collaborative, multidisciplinary approach to research, ecological risk assessment, development of public policy, and decision making for each proposed application of a gene drive technology. General principles to guide responsible practices for gene drives from the laboratory setting through to field release and monitoring are embedded as recommendations throughout the report.

Opinion: Is CRISPR-based gene drive a biocontrol silver bullet or global conservation threat?

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Webber, BLR, S.; Edwards, O. R.,  Proceedings of the National Academy of Sciences of the United States of America,  112:10565-10567. 2015-01-09 00:00:00.
Scientists have recognized the potential for applying gene drive technologies to the control of invasive species for several years, yet debate about the application of gene drive has been primarily restricted to mosquitoes. Recent developments in clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 technology have restarted discussions of using gene drive for invasive species control.

Safeguarding gene drive experiments in the laboratory

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Akbari, OSB, H. J.; Bier, E.; Bullock, S. L.; Burt, A.; Church, G. M.; Cook, K. R.; Duchek, P.; Edwards, O. R.; Esvelt, K. M.; Gantz, V. M.; Golic, K. G.; Gratz, S. J.; Harrison, M. M.; Hayes, K. R.; James, A. A.; Kaufman, T. C.; Knoblich, J.; Malik, H. S.; Matthews, K. A.; O'Connor-Giles, K. M.; Parks, A. L.; Perrimon, N.; Port, F.; Russell, S.; Ueda, R.; Wildonger, J.,  Science,  349:927-929. 2015-01-05 00:00:00.
Gene drive systems promote the spread of genetic elements through populations by assuring they are inherited more often than Mendelian segregation would predict (see the figure). Natural examples of gene drive from Drosophila include sex-ratio meiotic drive, segregation distortion, and replicative transposition. Synthetic drive systems based on selective embryonic lethality or homing endonucleases have been described previously in Drosophila melanogaster (1–3), but they are difficult to build or are limited to transgenic populations. In contrast, RNAguided gene drives based on the CRISPR/Cas9 nuclease can, in principle, be constructed by any laboratory capable of making transgenic organisms (4). They have tremendous potential to address global problems in health, agriculture, and conservation, but their capacity to alter wild populations outside the laboratory demands caution (4–7). Just as researchers working with self-propagating pathogens must ensure that these agents do not escape to the outside world, scientists working in the laboratory with gene drive constructs are responsible for keeping them confined (4, 6, 7).

Concerning RNA-guided gene drives for the alteration of wild populations

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Esvelt, KMS, Andrea L.; Catteruccia, Flaminia; Church, George M.,  eLife,  3:e03401. 2014-01-17 00:00:00.
Gene drives may be capable of addressing ecological problems by altering entire; populations of wild organisms, but their use has remained largely theoretical due to technical; constraints. Here we consider the potential for RNA-guided gene drives based on the CRISPR; nuclease Cas9 to serve as a general method for spreading altered traits through wild populations; over many generations. We detail likely capabilities, discuss limitations, and provide novel; precautionary strategies to control the spread of gene drives and reverse genomic changes. The; ability to edit populations of sexual species would offer substantial benefits to humanity and the; environment. For example, RNA-guided gene drives could potentially prevent the spread of; disease, support agriculture by reversing pesticide and herbicide resistance in insects and weeds,; and control damaging invasive species. However, the possibility of unwanted ecological effects and; near-certainty of spread across political borders demand careful assessment of each potential; application. We call for thoughtful, inclusive, and well-informed public discussions to explore the; responsible use of this currently theoretical technology.

The Sterile Insect Technique: can established technology beat malaria?

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M. E. H. Helinski, B. El-Sayed and B. G. J. Knols,  Entomologische Berichten,  66:13-20. 2006-06-06 14:48:37.
The Sterile Insect Technique (SIT) is the mass production, sterilisation and subsequent release of sterile insects into a target population in an area-wide integrated approach. The released sterile males mate with wild females; they thus no longer produce offspring and therefore the size of the target population is reduced. Over the years, SIT has proven to be a safe, effective and environmentally sound method to suppress, eliminate or contain pest populations. The International Atomic Energy Agency (IAEA) has a long history of supporting SIT programmes against key insect pests, including fruit flies, tsetse flies and moths. Recently, an integrated five year study to assess the feasibility of SIT to control African malaria mosquitoes has been initiated. In this article, we discuss the components and research requirements for such a feasibility study including sexing, mass production, sterilisation and release methodologies.

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