Working through the issues: Science, ethics and governance of gene drive research

The Committee on Gene Drive Research in Non-Human Organisms convened by National Academies of Sciences, Engineering, and Medicine held an information gathering meeting on October 28, 2015, to consider the Science, Ethics and Governance Considerations for Gene Drive Research.  This meeting comes as a component of a large Gene Drive study, which is set to review the state of the science of gene drive research that relies on genome editing techniques, such as CRISPR/Cas9 and other endonucleases or other genetic modification approaches, focusing on identifying the key scientific techniques for reducing ecological and other risks that should be considered prior to field releases of organisms carrying gene drives.

Committee co-chairs Elizabeth Heitman (Vanderbilt University) and James Collins (Arizona State University) opened the workshop by outlining the purpose of the Gene Drive Study and the objectives for the day. This was followed by a scientific discussion where Austin Burt, professor of evolutionary genetics at Imperial College London and co-author of Genes in Conflict, an extensive review of the biology of gene drive systems, gave a sweeping overview on the current state of the field and the possibilities and challenges of gene drives. Burt cautioned the committee to remember that gene drives release an organism into the environment, not just a single gene. To inform the committee on engineered nucleases, Shengdar Tsai, a postdoctoral scientist in Keith Joung’s lab at Massachusetts General Hospital and Harvard Medical School, shared experience with defining and identifying off-target sites, stating that “in some cases, off target sites can be cleaved with equal or higher frequency than on-target sites.” He also showed evidence that in silico methods fail to predict a majority of off-target cleavage sites and urged the committee to empirically assess the genome-wide potential for gene drive applications.

The scientific discussion closed with a conversation on the ecological and evolutionary conditions for gene flow led by Allison Snow, professor in the Department of Evolution, Ecology, and Organismal Biology at The Ohio State University and GSA member Nora Besansky, O’Hara Professor of Biology at the University of Notre Dame. Snow posed a central unknown question: Where will genes go and what happens if they get into the wild, underscoring the dearth of experience the field has with gene flow in plants outside of a small number of genetically engineered crops. She cited several key risks to avoid and called for an environmental risk assessment for each gene drive application to include information on reproductive rates, gene flow, potential for long distance dispersal, expected ecological and evolutionary effects, and level of uncertainty for predicting outcomes. Bersansky echoed the sentiments of Dr. Snow, noting that gene flow is a rare occurrence in multicellular animals, but it’s negative implications should not be underemphasized.

Four speakers were invited to present ethical considerations. The first, Francis Macrina, vice president for research at Virginia Commonwealth University, asserted the need for education to promote responsible research in gene drives, a reliance on scientific expertise to develop regulations, and a sense of shared responsibility among investigators, regulators, institutions, and publishers. The second speaker, Bruce Jennings, Director of Bioethics at the Center for Humans & Nature, suggested that the committee carefully conceptualize the power of gene drive technology (and upon whom it is imposed) to draw ethical criteria for governance. He further argues that we should place gene drive regulation in the broader context of global biotechnology regulation.  The final pair of talks on this topic where presented by Andrew Light, director, and Jesse Kilpatrick, assistant director, of the Institute for Philosophy and Public Policy at George Mason University. Their joint presentation brought forward the dichotomy of extrinsic considerations—such as safety, potential risk, and hazards—versus intrinsic considerations—such as whether gene drives are good for humanity and moral questions of “playing god.” Light and Kilpatrick recommended that the committee look for opportunities to bring moral and factual arguments together, using less polarizing language in public forums to help build consensus around the ethics of gene drive.

Because gene drives have clear applications in low and middle income countries, the committee invited Diran Makinde, director of the New Partnership for Africa’s Development Planning and Coordination Agency; Wannapa Suwonkerd, assistant director of the Office of Disease Prevention and Control in the Office of Administrative Health in Thailand; and Norma Padilla, director of the Center for Health Studies at the Universidad del Valle de Guatemala. Each of these speakers provided case studies for successful partnerships between researchers and local communities to reduce the prevalence of vector born diseases like malaria in their respective countries, highlighting the need for better training of local scientists who have ties to the community. The presenters also addressed the need for the scientific community to establish trust in areas where they plan to implement gene drive tests.

The final talks of the day focused on the broader topic of scales of governance for biotechnology. David Wirth, professor of law at Boston College, gave an overview of mechanisms to govern biotechnology, carefully noting that there is no clear regulation on an international scale. Megan Palmer, senior research scholar and Willam J. Perry Fellow in International Security at the Center for International Security and Cooperation at Stanford University, discussed U.S. governance of biotechnology, focusing on the gaps in implementation once oversight is in place. She urged the committee to think about how emerging technology shapes who has the capacity and power to govern and underlined the need to develop systems to manage and monitor the impact of biotechnology regulations. Zach Adelman, associate professor of entomology at Virginia Tech, shared his experiences in institutional governance, noting that existing NIH guidelines require institutional biosafety committees, which could regulate most laboratory gene drive experiments.

During the public comment period, GSA offered the following suggestions to the committee:

On behalf of the more than 5,500 members of the Genetics Society of America, many of whom have utilized gene editing technology in model organisms for decades, we are pleased to see the clear incorporation of scientific evidence into your considerations for the science, ethics, and governance of gene drive research.

To that end, we encourage the committee to continue to look closely to the model organism genetics community for information about the impact of genetic modification on populations. Indeed, these researchers’ experiences can calibrate the appropriate ethical responses to the scientific potential of gene drive research and its implications for society.

We are concerned that much of the public debate around these issues has not fully considered the actual scientific evidence on the safety and efficacy of genome editing and gene drive approaches. However, we are hopeful that this committee will [continue to] approach these issues with the appropriate regard for the peer-reviewed scientific literature and the expertise of researchers familiar with these process.

We therefore encourage the committee to continue to look to the model organism genetics community, incorporating their broad knowledge base of evolution, behavior, and reproduction as it moves toward recommendations for responsible Gene Drive Research.

The Genetics Society of America stands ready to work with the committee as you continue through the study process.

The entire workshop is available to view online.  Additional coverage on gene drives is available from Science magazine and NPR.

Relevant reading on Genes to Genomes:

Using genetic manipulation to fight disease