Posted by Bruce Jennings on Monday, July 4, 2016 in Blog.

From Paris last year came the news of mute violence bent on causing death, and a few weeks later came answering news of spoken global consensus on climate action bent on preserving life. Terror was answered by hope. Those who would be president of the United States spoke at length about the terrorist attack in Paris, and some of them, seeking to turn it to political advantage, seemed to relish stoking the fear it provoked. Much less was said by the candidates about the climate change accord, and many pointedly ignored it, as if they could not comprehend the kind of terrorism climate change represents, and as if they were unwilling to countenance any agreement that broke new ground, even one that provides only promises—voluntary “commitments”—not yet kept. This does not bode well for civic and moral learning in 2016.

So this is a good time to ask: What are the prospects for expanding the moral imagination and reviving a sense of ethical responsibility? I mean responsibility not only for malicious and malevolent conduct, but also, and especially, for collective actions that exemplify the best intentions and some of the most admirable traits of our species. Responsibility for governing good conduct is an important question because it is often when humans are at their best that the consequences of their intellect and collective powers are most perilous.

By “moral imagination” I do not mean make-believe or fantasy, but rather the capacity to take a critical distance from the given; to think reality otherwise in light of ethical norms and ideals. The moral imagination enables one to see connections between factors at work in history, in large social and cultural structures, and in the shape of one’s own life, thoughts, and feelings. The pertinence of this to environmental and conservation issues is manifest.

Moreover, by cultivating the moral imagination I mean developing the capability to recognize connection, interdependence, and symbiosis in natural and social life. By cultivating responsibility I do not mean primarily instilling a sense of blame or accountability, but rather inculcating the ability to respond appropriately. Imagination and responsibility go hand in hand to foster initial right recognition—recognition of injustice or of the true sources of reactionary fear or climate crisis denial, for instance—and answering right response—constructive, inclusive, empowering response.

The prospects for cultivating moral imagination and responsibility are in question—and have never been more vital—precisely because we have entered an era of human biopower. Extinction and loss of biodiversity—a massive culling and biotic simplification—is one pervasive and dramatic illustration of this. Global climate change is another as the life paths of plants and animals are deeply affected in even the most remote locations on earth. Virtually nothing is untouched by human hands, as the saying goes, any longer. Nothing is truly wild, if we mean by that unmolded rather than unruly. Nothing is really natural, if by natural we mean something that is governed by an impulse intrinsic to its own kind and type of being, rather than being shaped and used according to its extrinsic, instrumental value to humans.
It is important to recognize that the human technological shaping of nature on the regional scale of biodiversity loss, or on the planetary scale of climate change, is mirrored by its manifestation on the molecular and cellular scale through genomic engineering and biotechnology. We live in the age of human micro-biopower as well as macro-biopower, and we are on the cusp of intervening in the evolutionary process itself by using what might be called “techniques and technologies of unnatural selection.” By bringing forth the evolution of the human brain and cultural being, natural selection has made life on Earth susceptible to another, anthropogenic mode of evolution. This second evolution is driven by human will, scientific knowledge, and manipulative technology.

It has taken a long time, but it does appear that human beings have finally come to understand many of the basic properties and systemic features of reproduction, inheritance, genetic expression, cell metabolism, and the like. Homo sapiens has been probing the secrets of life through the domestication of plants and animals for at least five thousand years, but arguably in the last century or so we have gone further and faster in increasing human biopower than in all the previous millennia. We have always been creatures who create in various ways, but at last we stand poised on the threshold of intervening in the evolutionary process of whole species, including our own. A dream come true for some, perhaps a nightmare to others.

In 2010 a powerful and precise new technique of altering the DNA sequence using a protein called CRISPR-Cas9 was developed that is considerably more precise, effective, and facile than previous modes of gene splicing, using recombinant DNA (r-DNA) techniques and other means first developed in the 1970s. The newly developed gene editing capability arose from the study of bacteria whose immune response protects them from invading viruses, using proteins that provide resistance by cutting their DNA. One application of this, demonstrated in 2007, was the immunization of lactic acid bacteria against phages, which has important uses in the dairy industry. At first, attempts to initiate and control this process in the laboratory were not very precise or effective, but further research has demonstrated that CRISPR-Cas9, guided by associated RNA, can be made to cut the nuclear DNA at a designated location, thereby bringing about a specific genomic change in a cell. Technically, this is much easier and less expensive to accomplish than ever before, and its application is going viral, one might say, in research laboratories around the world. It is a tool that will greatly enhance understanding of basic biological mechanisms, and it will open new doors to many practical applications on nonhuman plants and animals, and in human medicine as well. Editing somatic cells in this way will alter the genetic functioning of an individual organism; editing a germ line cell will alter successive generations of offspring who inherit the anthropogenic trait.

As if this weren’t enough, there is another new development in biotechnology known as “gene drives.” By encoding the CRISPR mechanism and a particular DNA sequence in the reproductive cells of an organism, we could greatly increase the probability that certain traits will in fact be replicated by offspring and continue to be propagated in subsequent generations. Dominant genes will not be the result of fitness or environmental adaptation; we will select them. This not only stacks the deck of evolution, it greatly speeds it up. It can drive a particular genetic characteristic through the genotypes and phenotypes of an entire species within a few generations, a very short time for some creatures with rapid sexual maturity. It can also be a platform for deliberate extirpation of an entire species by altering its sexual balance (e.g. insuring that mostly males are born), resulting eventually in severe population decline. At the same time as we are talking about using genetic engineering to bring back simulacrums of lost species (de-extinction), we also have the prospect of rendering currently all too viable species extinct or scarce, if they bring harm to human health or pocketbooks.

In sum, decades of research on gene sequencing and mapping have taught us how to read the book of life, and from being readers, we have moved on to become editors, and we are using our blue pencil to revise the story of life more and more facilely. As the result of a summit conference held by the National Academies of Sciences, Engineering and Medicine last month, where restrictions and a moratorium on the use of CRISPR-Cas9 in human beings were proclaimed, media attention has focused on gene editing.
Before we get too worked up, past experience suggests that we should take this hype with a grain of salt. There is a tendency to exaggerate the efficacy of gene transfer technology, by immediately referring to it as “therapy” for terrible genetic diseases. So far, even though it is getting faster and easier, editing DNA alone has not turned out to be the magic bullet initially promised. CRISPR-Cas9 manipulates, but does not fundamentally reduce the complexity of most genetic diseases, which involve multiple gene loci and many factors affecting expression and penetrance (severity and manifestation in the phenotype). Indeed since the inception of the Human Genome Project in the 1990s, through years of research on the pathway from the DNA code to the chemical expression of that code in biochemical and metabolic processes and functions, science has found a very complex epigenetic system of gene-environment interactions and emergent properties, not the straightforward causal and reductionistic process that some scientists had expected.

In view of this it is interesting that so much attention is given to the potentially positive consequences of a new biotechnology in comparison to its potentially negative ones. And when bad consequences are discussed they are mainly defined in terms of human utility—direct or indirect harm to human health and interests. This anthropocentric default assumption at work in the selectivity of our bioethical concern deserves further comment. Aside from intervening to redirect the evolutionary process of certain species, this is a second form of unnatural selection, in my view.

While there has been a great deal of focus on the use of gene editing in human beings, the nonhuman environmental uses are being promoted and welcomed quite widely with open arms. As the headline in a recent New York Times report on the subject put it: “Open Season Is Seen in Gene Editing of Animals.” Bruce Whitelaw, a researcher at the Roslin Institute of the University of Edinburgh, observes, “We are going to see a stream of edited animals coming through because it’s so easy.” Because it is so easy? Is that all there is to it? The federal government recently approved for human consumption a type of salmon genetically modified to grow to market size more rapidly. Many other applications are being investigated, including GM pigs that are resistant to African swine fever and can be fattened with less food, chickens that produce only female offspring to increase egg yield, beef cattle that produce more muscle, and dairy cattle without horns. Surveying all this, Scott Fahrenkrug, CEO of a company called Recombinetics, explains that gene editing and gene drives are “like a find-replace function in the genome of these animals. It allows us to find the natural variation that exists across a species and quickly bring it under one hood.”

Moreover, we have not only an assumption of instrumental value at work in this narrative, but also a strikingly mechanistic set of metaphors to describe genomic, metabolic, and natural form and function. Biochemists speak of genomic “Lego blocks” and “cassettes,” and they draw analogues from computer software. These may comprise a convenient verbal short hand, but at the very least they convey the misleading suggestion that particular interventions in the genome can be discrete (the belief that we can do just one thing biologically), and they foster an illusion of causal control. And if these metaphors are taken seriously they can implicitly shape conceptual understandings—what the philosopher of science Michael Polanyi called “tacit knowledge”—that fly in the face of what epigenomics has actually taught us about the vibrant matter of complex living systems.

CRISPR-Cas9 does things that may superficially resemble the find and replace function of word processing programs, but we do not yet have an understanding of its underlying mechanisms. When we do, chances are that gene “editing” will not turn out to be analogous to word processing at all because genetic engineering and software engineering involve two quite different relationships between human design and the properties of the natural media (electrons and micro-circuitry vs. DNA, RNA, enzymes, and proteins) through which that design is operationalized. (What the future of Artificial Intelligence holds is another matter. That field may well come to draw its self-conscious metaphors from epigenetics, rather than the other way around.)

Nonetheless, gene editing and gene drives clearly raise important questions about moral imagination and responsibility—about precautionary government regulation of scientific research and commercial technological applications that pose great uncertainty and potential severe and irreversible risk to health and to the environment. Here I would like to offer some thoughts on how an ecological imagination and responsibility may be able to inform policy and regulation concerning gene editing.

I suggest that the most fundamental question for science policy concerning gene editing and gene drives goes beyond the issues of assessing potential risk and the distribution of benefits and burdens or utilities served. These are not unimportant questions, mind you. These technologies can probably be weaponized. There is the financial juggernaut of the bioeconomy and the pharmaceutical industry to be reckoned with. Like climate change, biotechnology and bioscience are global phenomena that will require international regulation and global governance. Nonetheless, the fundamental and underlying question is: What is the “right relationship” between human agency and the rest of nature? How should human beings relate to nature through science, not only instrumentally for the sake of their own interests, but also intrinsically as a matter of obligation derived from the fundamental conditions and nexus of life?

One answer to the question of right relationship is the anthropocentric utilitarian answer, which sees evolved species and ecosystems as flawed legacies to be corrected and improved upon. Another is an ecocentric answer for which evolved biophysical systems, when scientifically well-understood, are places of dynamic finitude and constrained becoming. Such places present human beings with duties of wise use and freedoms of flourishing and self-development in and through relationships of accommodation with the limits and the gifts of evolved nature. The ecocentric answer holds that value in the world resides in the natural and biotic context of which human individuals and societies are a part.

From an ecocentric perspective, right relationship is symbiotic with right self-recognition of human beings as fellow members of biotic communities with other species. Part and parcel of that membership are ecosystemic constraints and the inheritance of what the historical, probabilistic rhythms of evolution have produced in the time of our lives. Therefore, there is a natural standard of ethical rights and duties in how human beings and non-human beings should be treated. And there is a natural good toward which human action should strive that is inherent within systems of interdependence, relationship, sustainability, and resilience.

Can anything like this ecological moral imagination and sense of responsibility come to inform science policy concerning gene editing and gene drives? I believe that the answer is yes. I believe, moreover, that a science policy so informed would not necessarily prohibit the use of gene editing and gene drives in human and environmental applications entirely, but it would govern them with civic precaution and humility.

In order to see if this is true, and in order to achieve this kind of responsible innovation in science and technology, however, we will have to depart from past patterns of biotechnology policy, such as the narrow focus on human health threats and the containment and safety approaches that were the response to r-DNA technology in the 1970s. This was top-down governance and a successful attempt by the scientific and research community to display ethical responsibility so as to fend off the more extensive governmental regulation and control that might have erupted out of public fear and concern at the time.
This time around we need to do more than pay lip service to public engagement and democratic deliberation. We need to discuss and develop a new governance regime of civically responsible innovation, rather than relying on either an exclusively consequentialist ethical appraisal by experts or a populist ethical appraisal by consumers. And we need to do this soon, before the transfer of this technology from the laboratory into the marketplace becomes too wide-spread to manage.

What I am calling civic governance taps into non-elite sources of grounded knowledge and expertise that can mitigate the blind spots of top-down appraisals and provide early warnings that scientific innovators or commercial enterprises might have overlooked. The discussions of r-DNA techniques, for example, completely overlooked the coming global controversy over GM foods.

Also, a civic approach to technology innovation does not call for merely populist input or the more complete mobilization of interest group stakeholders. These lead to a kind of horse-trading and squeaky wheel type of governance or to regulatory capture by powerful vested interests. The civic model calls for bringing citizens together in new ways and with a new orientation guiding them as they clarify factual information, assess various scenarios under conditions of complexity and uncertainty, and exchange arguments and give reasons for various values and points of view. The point is to discern together what the common good and the individual rights of a society consist in when it comes to the rules of use of a specific new form of human biopower.

Finally, it is important to stress not simply engagement, but active deliberative engagement as the goal and to remember that moving toward an ethically broader paradigm of responsible innovation requires not only new value concepts and perspectives, but also appropriate institutional settings for deliberation. Let’s be frank. The reason to call for public engagement is not simply to mollify and reassure the public that the technology is in good hands. Rather it is to educate and engender greater scientific and civic literacy in the public so that they will gain an enhanced substantive and critical understanding of the technology and will then be able to have a serious and constructive voice in determining how it should be used.

A value criterion for responsible innovation in science and technology has to do with the effect of an innovation and its dissemination on the health and integrity of “nature,” seen as a web of life. “Integrity” on this view has to do with the sustainability, resilience, and capacity for self-renewal of systems that have been shaped by a long process of evolutionary adaptation. A closely related question is what effect widespread use of a technology will have, epistemologically and emotionally, on a culture’s understanding of nature and humankind’s place in it. Does a technology enable or impede our ability to see ourselves as engaged in interdependent, ecosystemic transactions with the biophysical world, where we are responsible citizens or members, not lords and masters? Moreover, does the use of a particular technology—and the power it confers on those groups that profit from it or control it—tend to hamper a culture’s ability to learn from advances in scientific knowledge and make adjustments over time in the practices and technologies it supports? Consider the use, widespread and scientifically accepted in the nineteenth century, of certain kinds of physiognomic measuring devices for the recording of the cranial and bone structures of particular individuals or groups. This technology and the data it generated significantly reinforced cultural racism and provided it with “scientific” legitimacy. My point is that even if the underlying validity of the physiological differences being measured were granted, that would not necessarily have the last word on the question whether a society ought to sanction the use of such a technology.

This value perspective could bear in different ways on the governance of gene editing and gene drives and their applications to ecosystem health and conservation and to whole species evolutionary modification. From this perspective:

•Ecosystemic and conservation outcomes that support biodiversity, integrity, and resilient functioning would underscore the ethical acceptability of gene drives.

•In the future, genetic modification of food crops and species subject to loss of population genetic diversity may be undertaken for the purposes of climate change mitigation and adaptation. This may be a licit role for gene editing and gene drives for conservation purposes. But it is ironic, nonetheless. The consequences of artifice beget more of it; thus, thanks to the logic of compensation, human artifice feeds upon itself.

• The deliberate extinction of an entire species due to the pursuit of human aims, even if meritorious, would face series challenge from this perspective.

•Altering a species so that it would no longer be a vector of zoonotic human disease, on the other hand, might be acceptable, although we should not be entirely surprised if the parasite or disease organism in question were to find an alternative host for its life cycle. The elimination of white tailed deer, for example, would not necessarily put an end to Lyme disease.

•Always pertinent to the assessment of any new genomic technology for conservation or health purposes is a comparison of the effectiveness and ecological impact of alternative means to achieve similar ends. Perhaps some notion like a ladder of intervention would be appropriate here—measures with less impact on germline genetic modification and evolutionary impact would be favored over measures with higher impacts.

•Generally prudential governance favors interventions that are reversible and/or contained within controlled environments in case unintended side effects (such as ecosystemic disruptions triggered by modified species) appear over time; this would also caution against germ-line interventions. Gene drives present a challenge to this approach since the entire point of them is to ensure that the modification is spread as widely as possible in a population. There is no recall or failsafe provision in this system, although some scientists talk about developing a gene drive that would reverse what an earlier gene drive had driven.

It is my hope that a civic process of responsible technological innovation will bring to the surface humility rather than hype in the face of the limits of scientific knowledge—humility in the face of practical complexity and the limits of technological control; humility in the face of the sheer giveness, the proof of life, of evolved living systems; and even humility concerning the hubris involved with confident anthropogenic attempts to correct or enhance natural evolution. This value orientation includes concern to avoid biological risks and harms, but it also asks what impact (positive or negative) a particular technological innovation could have on normatively meaningful modes of human self-understanding.
Are we creators or creatures? Are we beings in control of the world, or beings who prosper by accommodating themselves to webs of symbiotic interdependencies? The interplay of perfecting and accommodating is not unique to human beings—perhaps it characterizes all forms of life on earth—but with humans these modes of being are distinctive, and our technology greatly expands their scale and effects. The creator perfects and redefines necessity; the creature creatively adapts to necessity and achieves a modus vivendi with it. Are we creators or creatures, and if both, how can we achieve the balance between them that might be called humility?

Wendell Berry calls for a “new, or a renewed, propriety in the study and the use of the living world.” He goes on to say that propriety is a word whose value comes from its reference to the fact that we are not alone. “The idea of propriety,” he observes, “makes an issue of the fittingness of our conduct to our place or circumstances. . .It acknowledges the always-pressing realities of context and of influence; we cannot speak or act or live out of context. . . .We are being measured, in other words, by a standard that we did not make and cannot destroy. It is by that standard, and only by that standard, that we know we are in a crisis in our relationship to nature.”

(From Minding Nature 9.1 Jan. 2016 at www.humansandnature.org)

Tags: ethics, gene drives, gene editing, science policy