Regulating Gene Drives

In “Gene Drives: New and Improved” (Issues, Winter 2020), Robert M. Friedman, John M. Marshall, and Omar S. Akbari provide a comprehensive and accessible update on the field of gene drive research. By reviewing the diversity of strategies for gene drives, their primary envisioned applications, and the state of cutting-edge research, the authors offer an efficient way to understand key developments since the publication in 2016 of Gene Drives on the Horizon, by the National Academies of Sciences, Engineering, and Medicine. Although gene drives are arguably still on the horizon—none has been deployed beyond the laboratory even as part of a controlled field trial—advances described in the authors’ update make the time horizon for decision-making even more urgent.

The article makes the important point that a policy perspective should consider gene drives not as a broad regulatory yes-or-no exercise, but as a “design challenge.” The authors suggest that key design questions involve performance characteristics, outcomes to avoid, and desired social outcomes. This makes good sense, but how do we get there?

Several studies about public attitudes toward gene drives offer some insight. But should the gene drive research community simply accept these public attitude measures and prioritize the designs that received the most support? Unfortunately, I don’t think it’s that simple.

Gene Drives on the Horizon dedicated full chapters to the questions of human values and public, stakeholder, and community engagement around gene drives. I was a member of the study committee. We defined engagement as “seeking and facilitating the sharing and exchange of knowledge, perspectives, and preferences between or among groups who often have differences in expertise, power, and values,” and we went so far as to claim that “the outcomes of engagement may be as crucial as the scientific outcomes to decisions about whether to release a gene-drive modified organism into the environment.” This suggests that one-way measures of public attitudes are insufficient to inform the complex “design challenge” of gene drives.

Just as scientists are investigating and developing the kinds of novel technical options for gene drives described by Friedman, Marshall, and Akbari, social scientists are exploring methods to organize meaningful engagement to inform the design and governance of gene drives. As one example, I convened a diverse group of stakeholders in a workshop with the technical research team of the Genetic Biocontrol of Invasive Rodents project in March 2019. Our discussions about the various design decisions inherent in laboratory studies, contained trials, and potential future field trials yielded new insights that inform the ongoing challenge of designing and deploying a gene drive mouse for conservation purposes. (See our report at https://research.ncsu.edu/ges/2019/06/workshop-report-gene-drive-mice/).

Our workshop called attention to the benefits of integrating the design challenges—technical, regulatory, and engagement—that surround gene drive research. Funders should recognize this complementarity and prioritize the support of interdisciplinary teams that take all such design challenges seriously. The complexity, power, and potential of gene drives demand that we integrate engagement, governance, and technical innovation.

Jason A. Delborne

Melvin Kranzberg, one of the founders of the Society for the History of Technology, is well known for developing the first law of technology: “Technology is neither good nor bad; nor is it neutral.” This formulation applies perfectly to the current discussions surrounding the development of engineered gene drives and their potential application to conservation.

Robert M. Friedman, John M. Marshall, and Omar S. Akbari provide an excellent summary of the science of engineered gene drives currently under way. They stress that the technology is not one thing, but an ever-growing set of approaches with different objectives and constraints. They also stress the need for public consultation and the need for developers to demonstrate both safety and effectiveness.

Over the past seven years I have been involved in a global effort to write an evidence-based assessment of the intersection between conservation practice and synthetic biology—including gene drives. This effort is sponsored by the International Union for Conservation of Nature (IUCN), a global organization with more than 1,300 members from over 170 countries. My experience indicates that this will be far from enough to create a public space that supports informed transparent work on gene drives. Though many people know nothing about gene drives—naturally or engineered—they will base their opinions on many factors, only one of which will be the quality of the science itself. But the strong negative public reaction identified by the IUCN effort supports the concept of “confirmation bias”; as the Yale law professor Daniel Kahan wrote in 2017 regarding the set of experiments, “The subjects are aggressively misinforming themselves by selectively crediting or discrediting evidence on what scientists believe in patterns that cohere with the positions associated with their group identities.” This is the reality of science today.

Science is important as a means of learning more about engineered gene drives and whether they have a future in society’s scientific tool box. In the face of calls for a global moratorium on all work on gene drives, the point that Kranzberg makes about technology never being neutral is critically important. Unfortunately, there is precious little opportunity for people to find documents such as Friedman, Marshall, and Akbari’s and the IUCN assessment, or others that take a different position, and to educate themselves and form an opinion. All gene drive science is political: there is no neutral ground. We must learn to operate, keen to the constraints and opportunities of how people pose and get answers to their legitimate questions. The natural world is waiting for humanity to determine the right answer about potential use of engineered drives.

Kent H. Redford

Friedman, Marshall, and Akbari argue that from a policy perspective, the evaluation of gene drives for use in pest management should be treated not as a yes-no vote on a given proposal, but as a “design challenge” in which the goal is to ensure that proposals align with desired societal outcomes. There are a variety of gene drive approaches in development, they point out, and different approaches may align with goals better in different cases.

This is a move in the right direction, but it could go farther, in two important ways. First, the authors seem to see the design challenge as a matter of maximizing benefits and minimizing potential harms, but that too is unduly narrow. Proposals to suppress, eliminate, or replace wild populations, perhaps entire species, raise questions that fall outside the quick math of cost-benefit calculations. For some people, at least, there are large questions here about the meaning of genomes, the integrity of species, and ideals for the human relationship to nature. Gene drive technologies are similar in this respect to other genetic technologies used in or proposed for agriculture, human health and enhancement, and environmental conservation. We tend to agree with the authors that some gene drive approaches might have “societally desired outcomes,” but we cannot talk meaningfully about those outcomes if we’re not taking on board a large range of questions about what outcomes we’re aiming for.

Second, to understand what the societally desired outcomes are, there needs to be a meaningful societal conversation about the outcomes. Friedman, Marshall, and Akbari call, somewhat obscurely, for “robust design dialogues among product developers, regulators, and other societal players.” The idea seems to be that experts and power brokers of various sorts will identify the societally desired outcomes. Ideally, we’d figure out what nonexperts and less powerful people think too. This probably means a formal public deliberation process of some sort—a process that creates conditions in which to learn what people think when they’re really thinking, as the theorist of public deliberation James Fishkin puts it. At the very least, it means ensuring that regulators are hearing from the public. Existing mechanisms for public consultation are probably inadequate for this task. We should consider the possibility of augmenting those processes with opportunities for formal public deliberation.

Gregory E. Kaebnick

Michael K. Gusmano

Carolyn Neuhaus

Karen Maschke

Ben Curran Wills

In their timely and accessible description of the current state of gene drive research, Friedman, Marshall, and Akbari importantly dispel the common misunderstanding that all gene drives have the same property of potentially spreading throughout a species range based on release of a small number of individuals with the gene drive trait. Indeed, a greater variety of gene drives have been proposed with properties conducive to localized or temporary spread than those geared toward unrestricted spread. For a number of reasons including ease of construction, products that could have unrestricted spread are closer to release than those expected to have only local spread. Although attention is rightfully focused on unrestricted drives, we should not lose sight of other gene drives that may be much more appropriate in specific cases.

As the authors indicated, most of the funding for gene drive research has come from philanthropies and governments, and most of the researchers in this field are university faculty, students, and postdocs. This is very different from the model for research and funding for crop and microbial products of genetic engineering. This is not surprising given that there is no typical business model for a product that self-perpetuates. Over a decade prior to the use of the CRISPR gene-editing technology, academic gene drive researchers were already meeting to discuss how to develop and release products in a socially responsible manner, and how to avoid the shadow cast on biotechnology by Big Ag. The presence at meetings of representatives from the one company, Oxitec, that was doing peripherally related work ratcheted up anxiety of researchers because of the public’s negative response to that company’s tactics.

With all the claims that followed the development of CRISPR-based gene drives in 2015, the field attracted much more attention from social scientists and ethicist, and their perspectives became clearly articulated in the important 2016 report Gene Drives on the Horizon, referred to by Friedman, Marshall, and Akbari. The Foundation for the National Institutes of Health, the Bill & Melinda Gates Foundation, and other funders then began a concerted effort to develop socially responsible policies to determine yes-no decisions along the path for testing specific gene drive products with unrestricted spread.

Target Malaria, primarily funded by the Gates Foundation and Open Philanthropy, developed a semiautonomous ethics committee (of which I am a member) and has ongoing engagement with local communities and with African government entities where gene drives may be tested and ultimately deployed. Even as some people criticize such efforts, we will need to ask what kind of engagement will be needed by future less-well-funded projects to attain ethically appropriate informed consent of communities, countries, and continents. There is certainly no magical percentage of people consenting that enables an obvious decision. There are tough deliberations ahead.

Given this situation, it is worth considering whether we would be on this same trajectory if locally limited gene drives were the first to be moved forward. In any event, it certainly behooves us to continue developing locally limited gene drives and to make sure that policy-makers and the public understand that they are an option.

Fred Gould