Ainslie identifies two possible motivational sources for resolve: “thinking categorically” and “intertemporal bargaining.” Ainslie opts for intertemporal bargaining, adding that thinking categorically has no motivational power. The most researched instance of willpower is remission from addiction. This literature shows that aspirations for a more desirable identity and comfortable lifestyle motivate remission. In other words, “thinking categorically” drives willpower.

Based on brain imaging findings, we present a model according to which addiction emerges as an imbalance in the information processing and integration among various brain circuits and functions. The dysfunctions reflect (a) decreased sensitivity of reward circuits, (b) enhanced sensitivity of memory circuits to conditioned expectations to drugs and drug cues, stress reactivity, and (c) negative mood, and a weakened control circuit. Although initial experimentation with a drug of abuse is largely a voluntary behavior, continued drug use can eventually (...) impair neuronal circuits in the brain that are involved in free will, turning drug use into an automatic compulsive behavior. The ability of addictive drugs to co‐opt neurotransmitter signals between neurons (including dopamine, glutamate, and GABA) modifies the function of different neuronal circuits, which begin to falter at different stages of an addiction trajectory. Upon exposure to the drug, drug cues or stress this results in unrestrained hyperactivation of the motivation/drive circuit that results in the compulsive drug intake that characterizes addiction. (shrink)

Gene drives are potentially ontologically and morally disruptive technologies. The potential to shape evolutionary processes and to eradicate (e.g. malaria-transmitting or invasive) populations raises ontological questions about evolution, nature, and wilderness. The transformative promises and perils of gene drives also raise pressing ethical and political concerns. The aim of this article is to arrive at a better understanding of the gene drive debate by analysing how ontological and moral assumptions are coproduced in this debate. Combining (...) philosophical analysis with a critical reading of the gene drive literature and an ethnographic study of two leading research groups, the article explores the hypothesis that the development of and debate about gene drives are characterized by a particular intervention-oriented mode of coproduction. Based on the results of this exploration, we highlight the need for a broadening of the perspective on gene drives in which empirical, moral, and ontological concerns are addressed explicitly in their interplay rather than in (disciplinary) isolation from each other. (shrink)

Gene drive technology has immense potential. The ability to bypass the laws of Mendelian inheritance and almost ensure the transmission of specific genetic material to future generations creates boundless possibilities. But alongside these boundless possibilities are major social and ethical issues. This article aims to introduce gene drive technology, some of its potential applications, and some of the social and ethical issues that arise during research into the technology. For example, is investigation into gene drives hubristic? (...) Would applications of gene drives count as technological fixes? Or does research into such a technology sit on a slippery slope or lock us in to its full‐scale use? Are there perverse effects of engaging in research, and, most importantly, who ought to be included in the decision‐making process regarding research and field trials? Understanding the basic ethical landscape of this technology will prove invaluable to the public, scientists, and policy‐makers as research moves forward. (shrink)

For the purposes of conservation or suppression of species, gene drive technology has significant potential. Theoretically speaking, with the release of even relatively few animals with gene drive systems in an ecosystem, beneficial or harmful genes could be introduced into the entire wild-type population of that species. Given the profound impact that gene drives could have on species and ecosystems, their use is a highly contentious issue. Communities and groups have differing beliefs about nature and its (...) conservation or preservation, as well as concerns about the ecological safety of the eradication, replacement or enhancement of particular species of animals by means of genetic engineering. For all those reasons, the rigorous regulation of insects and other animals with gene drive systems is crucial. In this paper, we consider the question of whether the United States Food and Drug Administration is prepared to effectively regulate insects and other animals with gene drives. (shrink)

1. Traditional conservation biology has focused on two goals: preserving and protecting biodiversity and ecosystem integrity (e.g., Noss, 2001; Soulé, 1985). When species go extinct, this reduces b...

In recent years, CRISPR-Cas9 has become one of the simplest and most cost-effective genetic engineering techniques among scientists and researchers aiming to alter genes in organisms. As Zika came to the fore as a global health crisis, many suggested the use of CRISPR-Cas9 gene drives in mosquitoes as a possible means to prevent the transmission of the virus without the need to subject humans to risky experimental treatments. This paper suggests that using gene drives or other (...) forms of genome editing in nonhumans (like mosquitos) for the purposes of disease prevention raises important issues about informed consent. Additionally, it examines the consequences this line of inquiry could have for the use of gene drives as a tool in public health and suggests that the guidance offered by informed consent protocols could help the scientific community deploy gene drives in a way that ensures that ongoing research is consistent with our ethical priorities. (shrink)

BackgroundGene drive technologies (GDTs) promote the rapid spread of a particular genetic element within a population of non-human organisms. Potential applications of GDTs include the control of insect vectors, invasive species and agricultural pests. Whether, and if so, under what conditions, GDTs should be deployed is hotly debated. Although broad stances in this debate have been described, the convictions that inform the moral views of the experts shaping these technologies and related policies have not been examined in depth in the (...) academic literature.MethodsIn this qualitative study, we interviewed GDT experts (n = 33) from different disciplines to identify and better understand their moral views regarding these technologies. The pseudonymized transcripts were analyzed thematically.ResultsThe respondents’ moral views were principally influenced by their attitudes towards (1) the uncertainty related to GDTs; (2) the alternatives to which they should be compared; and (3) the role humans should have in nature. Respondents agreed there is epistemic uncertainty related to GDTs, identified similar knowledge gaps, and stressed the importance of realistic expectations in discussions on GDTs. They disagreed about whether uncertainty provides a rationale to refrain from field trials (‘risks of intervention’ stance) or to proceed with phased testing to obtain more knowledge given the harms of the status quo (‘risks of non-intervention’ stance). With regards to alternatives to tackle vector-borne diseases, invasive species and agricultural pests, respondents disagreed about which alternatives should be considered (un)feasible and (in)sufficiently explored: conventional strategies (‘downstream solutions’ stance) or systematic changes to health care, political and agricultural systems (‘upstream solutions’ stance). Finally, respondents held different views on nature and whether the use of GDTs is compatible with humans’ role in nature (‘interference’ stance) or not (‘non-interference stance’).ConclusionsThis interview study helps to disentangle the debate on GDTs by providing a better understanding of the moral views of GDT experts. The obtained insights provide valuable stepping-stones for a constructive debate about underlying value conflicts and call attention to topics that deserve further (normative) reflection. Further evaluation of these issues can facilitate the debate on and responsible development of GDTs. (shrink)

Mosquito-borne diseases represent a significant global disease burden, and recent outbreaks of such diseases have led to calls to reduce mosquito populations. Furthermore, advances in ‘gene-drive’ technology have raised the prospect of eradicating certain species of mosquito via genetic modification. This technology has attracted a great deal of media attention, and the idea of using gene-drive technology to eradicate mosquitoes has been met with criticism in the public domain. In this paper, I shall dispel two moral objections that (...) have been raised in the public domain against the use of gene-drive technologies to eradicate mosquitoes. The first objection invokes the concept of the ‘sanctity of life’ in order to claim that we should not drive an animal to extinction. In response, I follow Peter Singer in raising doubts about general appeals to the sanctity of life, and argue that neither individual mosquitoes nor mosquitoes species considered holistically are appropriately described as bearing a significant degree of moral status. The second objection claims that seeking to eradicate mosquitoes amounts to displaying unacceptable degrees of hubris. Although I argue that this objection also fails, I conclude by claiming that it raises the important point that we need to acquire more empirical data about, inter alia, the likely effects of mosquito eradication on the ecosystem, and the likelihood of gene-drive technology successfully eradicating the intended mosquito species, in order to adequately inform our moral analysis of gene-drive technologies in this context. (shrink)

This chapter analyzes the ‘hard sell’ of genetically engineered (GE) mosquitoes with gene drives as the solution to mosquito-borne diseases. A defining characteristic of the aggressive sell of the bio-technology is the ‘biologization’ of the significant prevalence of mosquito-borne diseases in certain socio-economically marginalized regions of the global South. Specifically, hard sell narratives either minimize or ignore the structural, systemic factors that are partially responsible for the public health problem that the GE mosquitoes are intended to bio-solve. The (...) biologization of a public health problem that disproportionately affects low-income, marginalized populations in certain global South regions has epistemic, epidemiological, and gendered ethico-political costs. The primary focus of this chapter is two scientific papers by researchers with ties to Target Malaria, a research organization developing GE mosquitoes with gene drives as the solution to malaria in the global South. In the interest of a contextualized analysis of the hard sell of GE mosquitoes with gene drives in those scientific papers, this chapter examines the normative commitments of Target Malaria’s key backer, the Bill and Melinda Gates Foundation, a powerful private organization that currently dominates the global health governance stage. (shrink)

CRISPR-Cas9 genome editing can and has altered human genomes, bringing bioethical debates about this capability to the forefront of philosophical and policy considerations. Here, I consider the underexplored implications of CRISPR-Cas9 gene drives for heritable human genome editing. Modification gene drives applied to heritable human genome editing would introduce a novel form of involuntary eugenic practice that I term guerrilla eugenics. Once introduced into a genome, stealth genetic editing by a gene drive genetic element would (...) occur each subsequent generation irrespective of whether reproductive partners consent to it and irrespective of whether the genetic change confers any benefit. By overriding the ability to ‘opt in’ to genome editing, gene drives compromise the autonomy of carrier individuals and their reproductive partners to choose to use or avoid genome editing and impose additional burdens on those who hope to ‘opt out’ of further genome editing. High incidence of an initially rare gene drive in small human communities could occur within 200 years, with evolutionary fixation globally in a timeframe that is thousands of times sooner than achievable by non-drive germline editing. Following any introduction of heritable gene drives into human genomes, practices intended for surveillance or reversal also create fundamental ethical problems. Current policy guidelines do not comment explicitly on gene drives in humans. These considerations motivate an explicit moratorium as being warranted on gene drive development in heritable human genome editing. (shrink)

Gene drives are selfish genetic elements that use a variety of mechanisms to ensure they are transmitted to subsequent generations at greater than expected frequencies. Synthetic gene drives based on the clustered regularly interspersed palindromic repeats genome editing system have been proposed as a way to alter the genetic characteristics of natural populations of organisms relevant to the goals of public health, conservation, and agriculture. Here, we review the principles and potential applications of CRISPR drives, (...) as well as means proposed to prevent their uncontrolled spread. We also focus on recent work suggesting that factors such as natural genetic variation and inbreeding may represent substantial impediments to the propagation of CRISPR drives. CRISPR-based synthetic selfish genetic elements, or gene drives, have been proposed as a means by which to genetically alter natural populations to address issues in agriculture, conservation, and public health. We describe key concepts of CRISPR gene drives and limitations that must be addressed before their use in the wild. (shrink)

Within the domain of public health, vector-borne diseases are among the most vehemently discussed issues. Recent scientific breakthroughs in genome editing technology provided a solution to this issue in the form of a gene drive that might decrease and even eradicate vector-borne diseases. Gene drives are engineered, and designed genes that can break typical inheritance rules and be passed to almost all of the carrier’s offspring. This genome editing and gene drive technology has become a powerful (...) tool for ecological and environmental engineering, through which man can manipulate his surroundings, adjusting it to himself and directly mastering evolution and the ecosystem. Although the gene drive technology has been perceived as promising in the public health domain, ecological implications of its use are not to be underestimated. The primary aim of this paper is to overcome the ongoing discussion which mostly focuses on whether priority should be given to the environment or to public health, and to find an adequate answer and solution. In this quest to find the proper answer and solution, Pierre Teilhard de Chardin’s thought might be useful, especially his concepts of the biosphere and the noosphere which may provide some clarifications as to why we are at the moment so cautious with gene drive technology and how we need to move towards a better common future on earth. (shrink)

This article contends that the environmental release of genetically engineered (GE) animals with heritable traits that are patented will present a challenge to the efforts of nations and indigenous peoples to engage in self‐determination. The environmental release of such animals has been proposed on the grounds that they could function as public health tools or as solutions to the problem of agricultural insect pests. This article brings into focus two political‐economic‐legal problems that would arise with the environmental release of such (...) organisms. To address those challenges, it is proposed that nations considering the environmental release of GE animals must take into account the underlying circumstances and policy failures that motivate arguments for the use of the modified animals. Moreover, countries must recognize that the UN International Covenant on Civil and Political Rights and the UN International Covenant on Economic, Social and Cultural Rights place on them an obligation to ensure that GE animals with patented heritable traits are not released without the substantive consent of the nations or indigenous peoples that could be affected. (shrink)

Cas9/guide RNA (gRNA)‐based gene drive systems are expected to play a transformative role in malaria elimination efforts., whether through population modification, in which the drive system contains parasite‐refractory genes, or population suppression, in which the drive system induces a severe fitness load resulting in population decline or extinction. DNA sequence polymorphisms representing alternate alleles at gRNA target sites may confer a drive‐resistant phenotype in individuals carrying them. Modeling predicts that, for observed levels of SGV at potential target sites and (...) observed rates of de novo DRA formation, population modification strategies are uniquely resilient to DRAs. We conclude that gene drives can succeed when fitness costs incurred by drive‐carrying mosquitoes are low enough to prevent strong positive selection for DRAs produced de novo or as part of the SGV and that population modification strategies are less prone to failure due to drive resistance. (shrink)

Clustered regularly interspaced short palindromic repeats genome editing has already reinvented the direction of genetic and stem cell research. For more complex diseases it allows scientists to simultaneously create multiple genetic changes to a single cell. Technologies for correcting multiple mutations in an in vivo system are already in development. On the surface, the advent and use of gene editing technologies is a powerful tool to reduce human suffering by eradicating complex disease that has a genetic etiology. Gene (...) drives are CRISPR mediated alterations to genes that allow them to be passed on to subsequent populations at rates that approach one hundred per cent transmission. Therefore, from an anticipatory biomedical ethics perspective, it is possible to conceive gene drive being used with CRISPR to permanently ameliorate aberrant genes from wild-type populations containing mutations. However, there are also a number of possible side effects that could develop as the result of combining gene editing and gene drive technologies in an effort to eradicate complex diseases. In this paper, we critically analyse the hypothesis that the combination of CRISPR and gene drive will have a deleterious effect on human populations from an ethical perspective by developing an anticipatory ethical analysis of the implications for the use of CRISPR together with gene drive in humans. (shrink)

Despite widespread and worldwide efforts to eradicate vector-borne diseases such as malaria, these diseases continue to have an enormous negative impact on public health. For this reason, scientists are working on novel control strategies, such as gene drive technologies (GDTs). As GDT research advances, researchers are contemplating the potential next step of conducting field trials. An important point of discussion regarding these field trials relates to who should be informed, consulted, and involved in decision-making about their design and launch. (...) It is generally argued that community members have a particularly strong claim to be engaged, and yet, disagreement and lack of clarity exist about how this “community” should be defined and delineated. In this paper, we shed light on this “boundary problem”: the problem of determining how boundaries of inclusion and exclusion in (GDT) community engagement should be drawn. As our analysis demonstrates, the process of defining and delineating a community is itself normative. First, we explicate why it is important to define and delineate the community. Second, we demonstrate that different definitions of community are used and intermingled in the debate on GDTs, and argue in favor of distinguishing geographical, affected, cultural, and political communities. Finally, we propose initial guidance for deciding who should (not) be engaged in decision-making about GDT field trials, by arguing that the definition and delineation of the community should depend on the rationale for engagement and that the characteristics of the community itself can guide the effective design of community engagement strategies. (shrink)

Gene drive technologies (GDTs) have been proposed as a potential new way to alleviate the burden of malaria, yet have also raised ethical questions. A central ethical question regarding GDTs relates to whether it is morally permissible to intentionally modify or eradicate mosquitoes in this way and how the inherent worth of humans and non-human organisms should be factored into determining this. Existing analyses of this matter have thus far generally relied on anthropocentric and zoocentric perspectives and rejected an (...) individualist biocentric outlook in which all living organisms are taken to matter morally for their own sake. In this paper, we reconsider the implications of taking a biocentric approach and highlight nuances that may not be evident at first glance. First, we shortly discuss biocentric perspectives in general, and then outline Paul Taylor’s biocentric theory of respect for nature. Second, we explore how conflicting claims towards different organisms should be prioritised from this perspective and subsequently apply this to the context of malaria control using GDTs. Our ethical analysis shows that this context invokes the principle of self-defence, which could override the pro tanto concerns that a biocentrist would have against modifying malaria mosquitoes in this way if certain conditions are met. At the same time, the case study of GDTs underlines the relevance of previously posed questions and criticism regarding the internal consistency of Taylor’s egalitarian biocentrism. (shrink)

The development of the CRISPR/Cas9 gene editing system has generated new possibilities for the use of gene drive constructs to reduce or suppress mosquito populations to levels that do not support disease transmission. Despite this prospect, social resistance to genetically modified organisms remains high. Gene drive open field research thus raises important questions regarding what is owed to those who may not consent to such research, or those could be affected by the proposed research, but whose consent (...) is not solicited. The precise circumstances under which informed consent must be obtained, and from whom, requires careful consideration. Furthermore, appropriate engagement processes should be central to any introduction of genetically modified mosquitos in proposed target settings. In this work, international guidance documents on informed consent and engagement are reviewed and applied to the genetically modified mosquito research context. Five analogous research endeavours that involve area-wide / open field experiments are reviewed. The approach of each in respect to the solicitation of individual informed consent and community engagement are highlighted. While the solicitation of individual informed consent in host settings of gene drive field trials may not be possible or feasible in some instances, local community and stakeholder engagement will be key to building trust towards the proposed conduct of such research. In this regard, the approaches taken by investigators and sponsors of political science field research and weather modification field research should be avoided. Rather, proponents of gene drive field research should look to the Eliminate Dengue field trials, cluster randomised trials, and pragmatic clinical trials for guidance regarding how the solicitation of individual informed consent of host communities ought to be managed, and how these communities ought to be engaged. (shrink)

The development of the CRISPR/Cas9 gene editing system has generated new possibilities for the use of gene drive constructs to reduce or suppress mosquito populations to levels that do not support disease transmission. Despite this prospect, social resistance to genetically modified organisms remains high. Gene drive open field research thus raises important questions regarding what is owed to those who may not consent to such research, or those could be affected by the proposed research, but whose consent (...) is not solicited. The precise circumstances under which informed consent must be obtained, and from whom, requires careful consideration. Furthermore, appropriate engagement processes should be central to any introduction of genetically modified mosquitos in proposed target settings. In this work, international guidance documents on informed consent and engagement are reviewed and applied to the genetically modified mosquito research context. Five analogous research endeavours that involve area-wide / open field experiments are reviewed. The approach of each in respect to the solicitation of individual informed consent and community engagement are highlighted. While the solicitation of individual informed consent in host settings of gene drive field trials may not be possible or feasible in some instances, local community and stakeholder engagement will be key to building trust towards the proposed conduct of such research. In this regard, the approaches taken by investigators and sponsors of political science field research and weather modification field research should be avoided. Rather, proponents of gene drive field research should look to the Eliminate Dengue field trials, cluster randomised trials, and pragmatic clinical trials for guidance regarding how the solicitation of individual informed consent of host communities ought to be managed, and how these communities ought to be engaged. (shrink)

CRISPR Cas9-powered gene drive allows for the rapid alteration of malaria-causing mosquitoes to spread an infertility gene or resistance to malaria among their species. Malaria eradication would be a great boon to human health. But many are concerned with driving genetic changes through a natural species. This chapter catalogs objections to the use of gene drive in mosquitoes for eradicating malaria. In-principle objections to gene drive use are not compelling. The most urgent concerns are related to (...) the safety of the technology for the environment and human health. Philosophers play a critical role in working along scientists to develop risk/benefit models that weigh the reasons for and against gene drive to eradicate malaria based on our best scientific knowledge and rigorous normative reasoning. (shrink)

The Segregation Distorter (SD) system of Drosophila melanogaster is one the best‐characterized meiotic drive complexes known. SD gains an unfair transmission advantage through heterozygous SD/SD+ males by incapacitating SD+‐bearing spermatids so that virtually all progeny inherit SD. Segregation distorter (Sd), the primary distorting locus in the SD complex, is a truncated duplication of the RanGAP gene, a major regulator of the small GTPase Ran, which has several functions including the maintenance of the nucleocytoplasmic RanGTP concentration gradient that mediates nuclear (...) transport. The truncated Sd‐RanGAP protein is enzymatically active but mislocalizes to the nucleus where it somehow causes distortion. Here I present data consistent with the idea that wild‐type RanGAP, and possibly other loci able to influence the RanGTP gradient, has been caught up in an ancient genetic conflict that predates the SD complex. The legacy of this conflict could include the unexpectedly rapid evolution of nuclear transport‐related proteins, the accumulation of chromosomal inversions, the recruitment of gene duplications, and the turnover of repetitive sequences in the centric heterochromatin. BioEssays 29:386–391, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

Technologies like CRISPR and gene drives are ushering in a new era of genetic engineering, wherein the technical means to modify DNA are cheaper, faster, more accurate, more widely accessible, and with more far-reaching effects than ever before. These cutting-edge technologies raise legal, ethical, cultural, and ecological questions that are so broad and consequential for both human and other-than-human life that they can be difficult to grasp. What is clear, however, is that the power to directly alter not (...) just a singular form of life but also the genetics of entire species and thus the composition of ecosystems is currently both inadequately regulated and undertheorized. In Gene Editing, Law, and the Environment, distinguished scholars from law, the life sciences, philosophy, environmental studies, science and technology studies, animal health, and religious studies examine what is at stake with these new biotechnologies for life and law, both human and beyond. (shrink)

How strong is the argument for requiring public deliberation by very large publics—at national or even global levels—before moving forward with efforts to use gene editing on wild populations of plants or animals? Should there be a general moratorium on any such efforts until such broad public deliberation has been successfully carried out? This article works toward recommendations about the need for and general framing of broad public deliberation. It finds that broad public deliberation is highly desirable but not (...) flatly necessary before moving forward with any local cases of gene editing in the wild. It also finds that broad public deliberation would be most helpful in generating very general guidance and is unlikely to be appropriate for specific cases. Broad public deliberation is most helpful for cases that involve higher levels of uncertainty and moral ambiguity, but separating out a distinct class of cases for deliberation is not yet possible. (shrink)

The placenta invades the adjacent uterus and controls the maternal immune system, like a cancer invades surrounding organs and suppresses the local immune response. Intriguingly, placental and cancer cells are globally hypomethylated and share an epigenetic phenomenon that is not well understood – they fail to silence repetitive DNA sequences that are silenced in healthy somatic cells. In the placenta, hypomethylation of retrotransposons has facilitated the evolution of new genes essential for placental function. In cancer, hypomethylation is thought to contribute (...) to activation of oncogenes, genomic instability, and retrotransposon unsilencing; the latter, we postulate, is possibly the most important consequence. Activation of placental retrotransposon-derived genes in cancer underpins our hypothesis that hypomethylation of these genes drives cancer cell invasion. This alludes to an interesting paradox, that while placental retrotransposon-derived genes are essential for promoting early hominid life, the same genes promote disease-susceptibility and death through cancer. Placental and cancer cells fail to silence retrotransposons that are normally silenced in healthy tissues. This has created new genes that are essential for placental function, yet they are also expressed in cancer. We hypothesize that active retrotransposons are a double-edged sword, contributing both adaptive and deleterious functions to biology. (shrink)

The release of genetically engineered organisms into the shared environment raises scientific, ethical, and societal issues. Using some form of democratic deliberation to provide the public with a voice on the policies that govern these technologies is important, but there has not been enough attention to how we should connect public deliberation to the existing regulatory process. Drawing on lessons from previous public deliberative efforts by U.S. federal agencies, we identify several practical issues that will need to be addressed if (...) relevant federal agencies are to undertake public deliberative activities to inform decision‐making about gene editing in the wild. We argue that, while agencies may have institutional capacity to undertake public deliberative activities, there may not be sufficient political support for them to do so. Advocates of public deliberation need to make a stronger case to Congress about why federal agencies should be encouraged and supported to conduct public deliberations. (shrink)

The article investigates the validity of two different versions of the slippery slope argument construed in relation to human gene therapy: the empirical and the conceptual argument. The empirical version holds that our accepting somatic cell therapy will eventually cause our accepting eugenic medical goals. The conceptual version holds that we are logically committed to accepting such goals once we have accepted somatic cell therapy. It is argued that neither the empirical nor the conceptual version of the argument can (...) provide a conclusive moral reason for banning somatic cell therapy. According to a third interpretation, referred to as the arbitrary result argument, the many apparent similarities between somatic cell therapy and eugenic-based human genetic engineering drive us to make principled choices concerning what differences and similarities between the two practices should be regarded as morally (ir)relevant. Decisions of this kind are likely to have unpredictable moral consequences. Thus formulated, the slippery slope argument has much plausibility. One objects to somatic cell therapy not so much because of what is at the bottom of the slope on which it lies, but because it is on a slope of which one does not know what is at the bottom. While the arbitrary result argument does not provide a conclusive reason for prohibiting human gene therapy, it reminds of a very important thing: when making bioethical decisions, we should be as specific and as consistent as possible about our basic moral and medical concepts. (shrink)

Although the field of psychiatry has witnessed the proliferation of studies on Gene x Environment (GxE) interactions, still limited is the knowledge we possess of GxE interactions regarding developmental disorders. In this perspective paper, we discuss why GxE interaction studies are needed to broaden our knowledge of developmental disorders. We also discuss the different roles of hazardous versus self-generated environmental factors and how these types of factors may differentially engage with an individual’s genetic background in predicting a resulting phenotype. (...) Then, we present exemplar studies that highlight the role of GxE in predicting atypical developmental trajectories as well as provide insight regarding treatment outcomes. Supported by these examples, we explicate the need to move beyond merely examining statistical interactions between genes and the environment, and to investigate specific genetic susceptibility and environmental contexts that drive developmental disorders. We propose that further parsing of genetic and environmental components is required to fully understand the unique contribution of each factor to the etiology of developmental disorders. Finally, with a greater appreciation of the complexities of GxE interaction, this discussion will converge upon the potential implications for clinical and translational research. (shrink)

Abstract: Many believe that, in addition to cognitive capacities, autonomous robots need something similar to affect. As in humans, affect, including specific emotions, would filter robot experience based on a set of goals, values, and interests. This narrows behavioral options and avoids combinatorial explosion or regress problems that challenge purely cognitive assessments in a continuously changing experiential field. Adding human-like affect to robots is not straightforward, however. Affect in organisms is an aspect of evolved biological systems, from the taxes of (...) single-cell organisms to the instincts, drives, feelings, moods, and emotions that focus human behavior through the mediation of hormones, pheromones, neurotransmitters, the autonomic nervous system, and key brain structures. We argue that human intelligence is intimately linked to biological affective systems and to the unique repertoire of potential behaviors, sometimes conflicting, they facilitate. Artificial affect is affect in name only and without genes and biological bodies, autonomous robots will lack the goals, interests, and value systems associated with human intelligence. We will take advantage of their general intelligence and expertise, but robots will not enter our intellectual world or apply for legal status in the community. -/- . (shrink)

Brussen, Kerri Anne A patent provides the exclusive legal right to a person or company to regulate the distribution, manufacture or use of their invention. This paper examines some of the issues surrounding Gene Patents. Although there is a drive to abolish Gene Patents, we argue that refined and clearly defined regulation would continue to support medical research, avoid exploitation, and be of benefit to public health.

Bio-art epitomizes a coalescence of art and sciences. It is an emerging contemporary artistic practice that uses a wide range of traditional artistic media interwoven with new artistic media that are biological in nature. This includes molecules, genes, cells, tissues, organs, living organisms, ecological niches, landscapes and ecosystems. In addition, bio-art expands into conceptual art using biological processes such as growth, cell division, photosynthesis and concepts of the origin of life and evolution, explaining them as new artistic media. In this (...) time of global challenges, bio-art communicates thoughts and feelings that involve relationships between the artist, science, public and the biological organism or biological concept. This article reviews the major challenges and driving forces that contributed to emerging biology-centered art and design. (shrink)

Most current techniques to deal with invasive species are ineffective or have highly damaging side effects. To this end suppression-drives based on clustered regularly inter-spaced short palindromic repeats (CRISPR/Cas9) have been touted as a potential silver bullet for the problem, allowing for a highly focused, humane and cost-effective means of removing a target species from an environment. Suppression-drives come with serious risks, however, such that the precautionary principle seems to warrant us not deploying this technology. The focus of (...) this paper is on one such risk – the danger of a suppression-drive escaping containment and wiping out the target species globally. Here, I argue that in most cases this risk is significant enough to warrant not using a gene-drive. In some cases, however, we can bypass the precautionary principle by using an approach that hinges on what I term the ‘Worst-Case Clause’. This clause, in turn, provides us with a litmus test that can be fruitfully used to determine what species are viable targets for suppression-drives in the wild. Using this metric in concert with other considerations, I suggest that only three species are currently possible viable targets – the European rabbit, ship rat and Caribbean Tree Frog. (shrink)

In this paper, we apply the perspective of intra-organismal ecology by investigating a family of ecological models suitable to describe a gene therapy to a particular metabolic disorder, the adenosine deaminase deficiency (ADA-SCID). The gene therapy is modeled as the prospective ecological invasion of an organ (here, bone marrow) by genetically modified stem cells, which then operate niche construction in the cellular environment by releasing an enzyme they synthesize. We show that depending on the chosen order (a choice (...) that cannot be made on \textit{a priori} assumptions), different kinds of dynamics are expected, possibly leading to different therapeutic strategies. This drives us to discuss several features of the extension of ecology to intra-organismal ecology. (shrink)

A gene's “expression profile” denotes the number of transcripts present relative to all other transcripts. The overall rate of transcript production is determined by transcription and RNA processing rates. While the speed of elongating RNA polymerase II has been characterized for many different genes and organisms, gene‐architectural features – primarily the number and length of exons and introns – have recently emerged as important regulatory players. Several new studies indicate that rapidly cycling cells constrain gene‐architecture toward short (...) genes with a few introns, allowing efficient expression during short cell cycles. In contrast, longer genes with long introns exhibit delayed expression, which can serve as timing mechanisms for patterning processes. These findings indicate that cell cycle constraints drive the evolution of gene‐architecture and shape the transcriptome of a given cell type. Furthermore, a tendency for short genes to be evolutionarily young hints at links between cellular constraints and the evolution of animal ontogeny. (shrink)

In The Selfish Gene, Richard Dawkins crystallized the gene's eye view of evolution developed by W.D. Hamilton and others. The book provoked widespread and heated debate. Written in part as a response, The Extended Phenotype gave a deeper clarification of the central concept of the gene as the unit of selection; but it did much more besides. In it, Dawkins extended the gene's eye view to argue that the genes that sit within an organism have an (...) influence that reaches out beyond the visible traits in that body - the phenotype - to the wider environment, which can include other individuals. So, for instance, the genes of the beaver drive it to gather twigs to produce the substantial physical structure of a dam; and the genes of the cuckoo chick produce effects that manipulate the behaviour of the host bird, making it nurture the intruder as one of its own. This notion of the extended phenotype has proved to be highly influential in the way we understand evolution and the natural world. It represents a key scientific contribution to evolutionary biology, and it continues to play an important role in research in the life sciences. The Extended Phenotype is a conceptually deep book that forms important reading for biologists and students. But Dawkins' clear exposition is accessible to all who are prepared to put in a little effort. Oxford Landmark Science books are 'must-read' classics of modern science writing which have crystallized big ideas, and shaped the way we think. (shrink)

An overview on archaeological evidence, provided by Colagè and d’Errico, reveals that the timing, location, and pace of cultural innovations are more consistent with scenarios that take culture, rather than genetic evolutionary processes, as the key driving force for human cognition. The authors elaborate on those mechanisms by which cultural evolution operates, with a specific focus on cultural exaptation and cultural neural reuse.

It is tempting to invoke organismal selection as perpetually optimizing the function of any given gene. However, natural selection can drive genic functional change without improvement of biochemical activity, even to the extinction of gene activity. Detrimental mutations can creep in owing to linkage with other selectively favored loci. Selection can promote functional degradation, irrespective of genetic drift, when adaptation occurs by loss of gene function. Even stabilizing selection on a trait can lead to divergence of the (...) underlying molecular constituents. Selfish genetic elements can also proliferate independent of any functional benefits to the host genome. Here we review the logic and evidence for these diverse processes acting in genome evolution. This collection of distinct evolutionary phenomena – while operating through easily understandable mechanisms – all contribute to the seemingly counterintuitive notion that maintenance or improvement of a gene's biochemical function sometimes do not determine its evolutionary fate. (shrink)

Proposals to release genetically engineered organisms in the wild raise complex ethical issues related to their safe and equitable implementation. While there is broad agreement that community and public engagement is vital to decision‐making in this context, more discussion is needed about who should be engaged in such activities and in what ways. This article identifies Indigenous peoples as key stakeholders in decisions about gene‐editing in the wild and argues that engagement activities need not only include Indigenous peoples but (...) also be designed, conducted, and analyzed in ways that confront longstanding power imbalances that dismiss Indigenous expertise. We offer specific recommendations to guide deliberative activities to not only be inclusive of Indigenous peoples but also to empower their diverse, situated knowledges. We call on those committed to the inclusive design of broad public deliberation to pursue strategies that shift dominant power dynamics to include Indigenous communities in more meaningful ways. (shrink)

Somatic diversification of antigen receptor genes depends on the activity of enzymes whose homologs participate in a mutagenic DNA repair in unicellular species. Indeed, by engaging error-prone polymerases, gap filling molecules and altered mismatch repair pathways, lymphocytes utilize conserved components of genomic stress response systems, which can already be found in bacteria and archaea. These ancient systems of mutagenesis and repair act to increase phenotypic diversity of microbial cell populations and operate to enhance their ability to produce fit variants during (...) stress. Coopted by lymphocytes, the ancient mutagenic processing systems retained their diversification functions instilling the adaptive immune cells with enhanced evolvability and defensive capacity to resist infection and damage. As reviewed here, the ubiquity and conserved character of specialized variation-generating mechanisms from bacteria to lymphocytes highlight the importance of these mechanisms for evolution of life in general. (shrink)

Environmental releases of gene edited (GEdOs) and gene drive organisms (GDOs) will likely occur under conditions of high uncertainty and in complex socioecological systems. Therefore, public deliberation is especially important to account for diverse interpretations of safety, risks, and benefits; to draw on experiential and public wisdom in areas of proposed release; to ameliorate dangers of technological optimism; and to increase the public legitimacy of decisions. Yet there is a “democratic deficit” in the United States' oversight system for (...) GEdOs and GDOs, as unconflicted experts, publics, and skeptical stakeholders are most often excluded from decision‐making and unavailable to critically examine potential risks and benefits or raise broader concerns about socioeconomic or cultural impacts. This article argues for the need to open up decision‐making for GEdOs and GDOs, discusses the challenges for doing so within the current oversight framework, and finally, proposes institutional, policy, and attitudinal changes that are likely important for overcoming barriers to public deliberation. (shrink)

Different cell lineages growing in microgravity undergo a spontaneous transition leading to the emergence of two distinct phenotypes. By returning these populations in a normal gravitational field, the two phenotypes collapse, recovering their original configuration. In this review, we hypothesize that, once the gravitational constraint is removed, the system freely explores its phenotypic space, while, when in a gravitational field, cells are “constrained” to adopt only one favored configuration. We suggest that the genome allows for a wide range of “possibilities” (...) but it is unable per se to choose among them: the emergence of a specific phenotype is enabled by physical constraints that drive the system toward a preferred solution. These findings may help in understanding how cells and tissues behave in both development and cancer. In microgravity, cells undergo spontaneous and reversible transitions between different phenotypes. In the absence of physical constraints, living systems could yield bi-stable decisions. On the contrary, physical ‘boundaries’ constrain cells to acquire only a specific configuration by selecting and shaping different gene expression patterns provided by the intrinsic genetic stochasticity. (shrink)

Theories of the genetics underlying punctuated equilibrium (PE) have been vague to date. Here the developmental gene hypothesis is proposed, which states that: 1) developmental regulatory (DevReg) genes are responsible for the orchestration of metazoan morphogenesis and their extreme conservation and mutation intolerance generates the equilibrium or stasis present throughout much of the fossil record and 2) the accumulation of regulatory elements and recombination within these same genes—often derived from transposable elements—drives punctuated bursts of morphological divergence and speciation (...) across metazoa. This two‐part hypothesis helps to explain the features that characterize PE, providing a theoretical genetic basis for the once‐controversial theory. Also see the video abstract here https://youtu.be/C-fu-ks5yDs. (shrink)