Gene Drives: Panacea or Pandora's Box?

From November 7-25th, States Parties to the Biological and Toxin Weapons Convention (BWC) are taking part in the treaty's Eighth Review Conference in Geneva. Review Conferences, which take place every five years, are the BWC's only decision-making bodies, and among other responsibilities review new scientific and technological developments relevant to the BWC. Among the new and powerful scientific developments in the life sciences that Conference participants will grapple with will be gene drive systems, which pose immense challenges and opportunities for the public health and biosecurity fields.[1]

Gene drive systems "drive" genes over successive generations through populations of organisms that, unlike bacteria and viruses, undergo sexual reproduction. Until recently, it was difficult for scientists to engineer a gene drive in laboratories because the available techniques were cumbersome.[2] The situation dramatically changed in 2009 when a widely applicable genome editing technique named CRISPR-Cas9 was developed. Beyond this technique's direct utility for the genomic modification of bacteria and viruses, the ability of CRISPR-Cas9 to precisely target sequences for genome editing provides scientists with an effective method to engineer synthetic gene drive systems in organisms that reproduce sexually.[3] If organisms modified to carry a gene drive system are released into the environment and reproduce with their wild counterparts, the percentage of the population with the chosen trait grows rapidly with subsequent generations. In organisms that reproduce often, such as mosquitoes, a large number of organisms endowed with the chosen trait can be rapidly engineered.

Explore the below interactive to learn more about gene drives.[4]

The ability to carry out gene drives in sexually reproducing organisms bestows scientists with a powerful tool to alter or potentially eliminate entire populations of organisms in the wild. For example, a gene drive can be designed so that female mosquitoes express infertility, thereby decreasing specific mosquito populations with each generation with infertile female mosquitoes, which could reduce the spread of mosquito-borne pathogens such as those that cause Zika, malaria, dengue, and yellow fever.[5,6] However, this ability to rapidly alter wild populations could also be misused, which poses novel security risks for entomological warfare, agro-sabotage, and ecocide.[7] For example, instead of spreading infertility in mosquitoes, a hostile actor could spread infertility among pollinators such as bees that are vital to a targeted country's agriculture.

If a country realizes that it has been the target of a malicious gene drive, given time its scientists may be able to deploy a gene drive that acts to reverse the change– a "reversal" drive. Detection of DNA coding for a Cas9 system in a wild organism would be a telltale sign that a drive has been released, but it is extremely doubtful that the DNA of organisms that could be targeted– be it fish or bees– are sequenced by scientists regularly enough to provide timely warning for the reversal drive to take effect. A reversal drive cannot bring dead organisms back to life. By the time it is deployed, the targeted population and the broader ecosystem it operates within may have suffered irreparable disruption.[8] A "reversal" drive also cannot remove the Cas9 component from the DNA of affected organisms, and the addition of this component might affect the health or behavior of modified organisms. A malicious gene drive that fails to achieve its goal, either because it was poorly designed or rapidly reversed, will still have irreparably changed the genetic makeup of organisms in the wild.

Developing a gene drive system, malicious or otherwise, is not trivial. Designing an effective gene drive requires specialized knowledge, and working with the organisms about to be edited can be difficult. Nevertheless, engineering a CRISPR-Cas9-enabled gene drive does not require specialized equipment. If an individual has an institutional affiliation, suitable CRISPR-Cas9 system components can be readily purchased from purveyors on the internet for a few hundred dollars. The growing availability of information about these techniques and the ease with which suitable equipment needed to apply them can be obtained raises the specter of incompetent or ill-willed persons accidentally or deliberately releasing organisms altered with gene drive systems into the environment.

The extent of the security threats posed by the developments in gene drive systems remains contested amongst experts, but the BWC is the appropriate international forum for this discussion. Although the potential for malicious gene drives has been briefly raised before at recent BWC meetings, the current conference framework has failed to produce a security risk assessment for gene drives, probably because the conference has few mechanisms to do so. The BWC lacks a mechanism similar to that of the Organisation for the Prohibition of Chemical Weapons' Scientific Advisory Board, which consists of experts from many different countries who meet to thoroughly assess and report on technology developments relevant to the Chemical Weapons Convention. As the Eighth Review Conference proceeds, its participants would do well to establish such a science advisory body that would be tasked to meet in a timely fashion to assess breakthroughs in the biosciences with likely relevance to the operations of the BWC.[9] Doing so would help ensure that the BWC continues to function effectively in the future.[10]

 


Sources:

[1] Kenneth A. Oye, “On Regulating Gene Drives: A New Technology for Engineering Populations in the Wild,” presentation to the Biological Weapons Convention Meeting of Experts, Session 4: Science and Technology Developments, August 6, 2014, Geneva, Switzerland; unog.ch/bwc/docs.

[2] Austin Burt, “Site-specific selfish genes as tools for the control and genetic engineering of natural populations,” Proc. Biol. Sci. 270, no. 1518 (May 7, 2003): p. 921-928.

[3] Kevin M. Esvelt et al., “Concerning RNA-guided gene drives for the alteration of wild populations,” eLife 3 (2014): p. 1-21.

[4] Elsa Abdoun, Émilie Rauscher, Yves Sciama, Caroline Tourbe, “Bricoleurs du Vivant: Pour Soigner, Créer, Optimiser… Ils Ont Trouvé Leur Outil!” [Tinkerers of the Living: To Heal, Create, Optimize… They Have Found Their Tool!] Science & Vie magazine, January 2016, p. 45-64.

[5] Andrew Hammond et al., “A CRISPR-Cas9 gene drive system targeting female reproduction in malaria mosquito vector Anopheles gambiae,” Nature Biotechnology 34, no. 1 (January 2016): p. 78-83.

[6] Alternatively, genes coding for antigens against a vector-borne disease could be inserted into the vector. Valentino M. Gantz et al., “Highly efficient Cas9-mediated gene drive for population modification of the malaria vector mosquito Anopheles stephensi,” PNAS 112, no. 49 (November 23, 2015): p. E6736-E6743.

[7] Kenneth A. Oye et al., “Regulating Gene Drives,” Science 345, no. 6197 (August 8, 2014): p. 626-628.

[8] Kevin Esvelt, “Gene Editing and Gene Drives,” presentation to the National Academies of Sciences, Engineering, and Medicine, Gene Drive Research on Non-Human Organisms: Recommendations for Responsible Conduct, July 30, 2015, Washington, U.S.A.; www.youtube.com.

[9] The Interacademy Partnership (IAP), “The Biological and Toxin Weapons Convention: Considerations for a Science Advisory Mechanism,” July 2016, p.1-15; www.interacademies.net.

[10] Filippa Lentzos, Gregory D. Koblentz, “It’s time to modernize the bioweapons convention,” Bulletin of the Atomic Scientists, November 4, 2016; thebulletin.org.

November 21, 2016
About

Gene drive systems pose immense challenges and opportunities for the public health and biosecurity fields.

Authors
Gabrielle Tarini

Research Associate, Center for Nonproliferation Studies

Raymond A. Zilinskas

Director, Chemical and Biological Weapons Nonproliferation Program, Center for Nonproliferation Studies

This material is produced independently for NTI by the James Martin Center for Nonproliferation Studies at the Middlebury Institute of International Studies at Monterey and does not necessarily reflect the opinions of and has not been independently verified by NTI or its directors, officers, employees, or agents. Copyright 2017.