This chapter contains sections titled: Promise and Disappointment Ethical Issues Resource Allocation References.

Duchenne's muscular dystrophy (DMD), which affects 1/3500 live male births, involves a progressive degeneration of skeletal and cardiac muscle, leading to early death. The protein dystrophin is lacking in DMD and present, but defective, in the allelic, less severe, Becker muscular dystrophy and is also missing in the mdx mouse. Experiments on the mdx mouse have suggested two possible therapies for these myopathies. Implantation of normal muscle precursor cells (mpc) into mdx skeletal muscle leads to the conversion of dystrophin‐negative (...) fibres to ‐positive, with consequent improvement in muscle histology. Direct injectidn of dystrophin cDNA into skeletal or cardiac muscle also gives rise to dystrophin‐positive fibres. Although both appear promising, there are a number of questions to be answered and refinements to be made before either technique could be considered possible as treatments for myopathies in man. (shrink)

Gene therapy and gene editing are revolutionising the treatment of genetic diseases, most notably haematological disorders. This paper evaluates the use of both techniques in hereditary blood disorders. Many studies have been conducted in this field, especially with gene therapy, with very promising results in diseases such as haemophilia, certain haemoglobinopathies and Fanconi anaemia. The application of these techniques in clinical practice and the foreseeable development of these approaches in the coming years suggest that it (...) might be useful to evaluate the results achieved thus far. It is also essential to reflect on the possible bioethical concerns raised by the use of both techniques, especially in terms of safety issues for patients, potential side effects, treatment duration, accessibility and cost of treatment, and the heritability of genetic changes produced if germline cells are used. (shrink)

Gene therapy approaches have great promise in the treatment of neurodegenerative disorders and malignant brain tumors. Neuwelt et al. review available viral-mediated gene therapy methods and their blood-brain-barrier (BBB) disruption delivery technique, briefly mentioning nonviral mediated gene therapy methods. This commentary discussed the BBB disruption delivery technique, viral and nonviral mediated gene therapy approaches to Parkinson's disease, and the potential use of antisense oligo to suppress malignant brain tumors.

It may be unethical to deny children with cystic fibrosis access to ethically approved clinical trials from which they might benefitDespite advances in nutritional management, aggressive antibiotic usage, and physiotherapy, cystic fibrosis remains a life limiting illness with high morbidity that imposes considerable burdens on children and families.1 Although survival to 40 years is predicted for children born in 1990s, the median age of death in 2003 was 24.2 years .The pathophysiological features of CF are produced by a defective (...) class='Hi'>gene on chromosome 7, resulting in the defective production of a protein that regulates cellular ion transport. Defective ion transport is thought to lead to increased mucus viscosity , with poor airway clearance, recurrent bacterial infection, lung damage, and death.Gene therapy , the insertion of a normally functioning gene into deficient host cells using a suitable vector, is a potential treatment or cure for diseases produced by single gene defects—for example, CF. Gene therapy does, however, have potential or actual risks, leading many to suggest that evidence of efficacy in adults should be demonstrated before trials are conducted in children. Many serious diseases in adults such as CF have their onset in childhood. If early treatment provides greater hopes of benefit, children may be more appropriate targets for GT in CF than adults. It may be unethical to deny them access to properly constructed, ethically approved clinical trials from which they might benefit.Since research in children should be scientifically valid, in the child’s best interests, and the subject of valid consent, this article will consider these parameters in relation to trials of GT in children with CF. Because of the importance of consumer participation in the design of research we present the results of a questionnaire about GT trials delivered …. (shrink)

Recombinant DNA technology will soon allow physicians an opportunity to carry out both somatic cell- and Germ-Line gene therapy. While somatic cell gene therapy raises no new ethical problems, gene therapy of gametes, fertilized eggs or early embryos does raise several novel concerns. The first issue discussed here relates to making a distinction between negative and positive eugenics; the second issue deals with the evolutionary consequences of lost genetic diversity. In distinguishing between positive (...) and negative eugenics, the concept of malady is applied as a definitional criterion for identifying genetic disorders that could qualify for Germ-Line therapy. Because gene replacement techniques are currently unavailable for humans, and because even if they were possible the number of people involved would be quite small, the loss of diversity concern seems moot. Finally, we dissuss the issue of iatrogenic disorders associated with gene therapy and discuss several ‘real world considerations.’. (shrink)

Somatic cell gene therapy has yielded promising results. If germ cell gene therapy can be developed, the promise is even greater: hundreds of genetic diseases might be virtually eliminated. But some claim the procedure is morally unacceptable. We thoroughly and sympathetically examine several possible reasons for this claim but find them inadequate. There is no moral reason, then, not to develop and employ germ-line gene therapy. Taking the offensive, we argue next that medicine has (...) a prima facie moral obligation to do so. (shrink)

The prelude to successful human somatic gene therapy, i.e. the efficient transfer and expression of a variety of human genes into target cells, has already been accomplished in several systems. Safe methods have been devised to do this using non‐viral and viral vectors. Potentially therapeutic genes have been transferred into many accessible cell types, including hematopoietic cells, hepatocytes and cancer cells, in several different approaches to ex vivo gene therapy. Successful in vivo gene therapy (...) requires improvements in tissuetargeting and new vector design, which are already being sought. Gene‐transfer protocols have been approved for human use in inherited diseases, cancer and acquired disorders. Althouth the results of these trials to date have been somewhat disappointing, human somatic cell gene therapy promises to be an effective addition to the arsenal of approaches to the therapy of many human diseases in the 21st century if not sooner. (shrink)

Gene therapy has emerged from the idea of inserting a wild‐type copy of a gene in order to restore the proper expression and function of a damaged gene. Initial efforts have focused on finding the proper vector and delivery method to introduce a corrected gene to the affected tissue or cell type. Even though these first attempts are clearly promising, seveal problems remain unsolved. A major problem is the influence of chromatin structure on transgene expression. (...) To overcome chromatin‐dependent repressive transgenic states, researchers have begun to use chromatin regulatory elements to drive transgene expression. Insulators or chromatin boundaries are able to protect a transgene against chromatin position effects at their genomic integration sites, and they are able to maintain transgene expression for long periods of time. Therefore, these elements may be very useful tools in gene therapy applications for ensuring high‐level and stable expression of transgenes. BioEssays 26:796–807, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

The field of regenerative medicine has considerable therapeutic promise that is proving difficult to realize. As a result, governments have supported the establishment of intermediary agencies to “accelerate” innovation. This article examines in detail one such agency, the United Kingdom’s Cell and Gene Therapy Catapult. We describe CGTC’s role as an accelerator agency and its value narrative, which combines both “health and wealth.” Drawing on the notion of sociotechnical imaginaries, we unpack the tensions within this narrative and its (...) instantiation as the CGTC cell therapy infrastructure is built and engages with other agencies, some of which have different priorities and roles to play within the RM field. (shrink)

: The medical and clinical promise of stem cell research is widely heralded, but moral judgments about it collide. This article takes general stock of such judgments and offers one specific resolution. It canvasses a spectrum of value judgments on sources, complicity, adult stem cells, and public and private contexts. It then examines how debates about abortion and stem cell research converge and diverge. Finally, it proposes to extend the principle of "nothing is lost" to current debates. This extension links (...) historic discussions of the ethics of direct killing with unprecedented possibilities that in vitro fertilization procedures yield. A definite normative region to inhabit is located, within a larger range of rival value judgments. The creation of embryos for research purposes only should be resisted, yet research on "excess" embryos is permissible by virtue of an appeal to the "nothing is lost" principle. (shrink)

Recombinant adeno‐associated viruses (rAAVs) are promising vectors for the delivery of various genetic constructs into eukaryotic cells. rAAVs have a number of properties that make it possible to successfully use them both in vitro and in vivo. Purification and concentration of rAAV vectors are critical for achieving high viral titer, stability, efficiency, and purity. This review systematically analyses all available purification approaches. The purification methods described in this work differ substantially from each other in mechanisms, efficiency, labor time, and cost. (...) Researchers have to choose a purification algorithm depending on the purpose of their work. We strive to simplify the choice of the necessary and sufficient technique based on the experimental needs and available resources of the laboratory. (shrink)

We all live our daily lives surrounded by the products of technology that make what we do simpler, faster, and more efficient. These are benefits we often just take for granted. But at the same time, as these products disburden us of unwanted tasks that consumed much time and effort in earlier eras, many of them also leave us more disengaged from our natural and even human surroundings. It is the task of what Gene Moriarty calls focal engineering to (...) create products that will achieve a balance between disburdenment and engagement: “How much disburdenment will be appropriate while still permitting an engagement that enriches one’s life, elevates the spirit, and calls forth a good life in a convivial society?” One of his examples of a focally engineered structure is the Golden Gate Bridge, which “draws people to it, enlivens and elevates the human spirit, and resonates with the world of its congenial setting. Humans, bridge, and world are in tune.” These values of engagement, enlivenment, and resonance are key to the normative approach Moriarty brings to the profession of engineering, which traditionally has focused mainly on technical measures of evaluation such as efficiency, productivity, objectivity, and precision. These measures, while important, look at the engineered product in a local and limited sense. But “from a broader perspective, what is locally benign may present serious moral problems,” undermining “social justice, environmental sustainability, and health and safety of affected parties.” It is this broader perspective that is championed by focal engineering, the subject of Part III of the book, which Moriarty contrasts with “modern” engineering in Part I and “pre-modern” engineering in Part II. (shrink)

This paper aims to persuade its reader that libertarianism, at least in several of its varieties, is a species of the genus Michael Oakeshott referred to as ‘rationalism in politics’. I hope to demonstrate, employing the work of Oakeshott, as well as Aristotle and Onora O’Neill, how many libertarian theorists, who generally have a sincere and admirable commitment to personal liberty, have been led astray by the rationalist promise that we might be able to approach deductive certainty concerning the 'correctness' (...) of some political programme. Of course libertarians, in common with the adherents of almost any other political ‘stance’, are not a monolithic body, but exhibit a variety of more or less rationalist arguments for their views. For example, a thinker like Hayek, who is often placed in the libertarian camp, came to adopt much of Oakeshott’s critique of rationalism in his later work. And, of course, Oakeshott himself expressed an affinity for libertarian ideas in his essay, ‘The Political Economy of Freedom’ (1991 [1962]). But a general predilection to enhance individual freedom as far as is deemed practicable is quite a different matter from taking a stance in which liberty, and liberty conceived in a rather narrow fashion, is the only value deemed admissible into ‘reasonable’ political discourse. (We will see in a subsequent section that Oakeshott recognized this urge to sanctify one value above all others as a logical requirement of striving for deductive political truths.) I believe that a critique of such libertarian rationalism is particularly relevant given the present situation in the United States vis-à-vis civil rights and the ongoing ‘war on terror’, in that many non- libertarian supporters of peace and strong civil rights find themselves allied with libertarians on these issues—if libertarians have gotten these issues ‘correct’, then how might they have gone wrong elsewhere? Furthermore, the critique may aid libertarians themselves, because, if the title of this paper is accurate, such a single-minded exaltation of one value above all others is an enemy of true liberty, so that libertarians might want to rethink adopting such a position. As Philip Pettit demonstrates (1997), freedom as non-domination is more robust and inclusive of all that we value about freedom than is the libertarian concept of freedom as non-interference; by allowing, say, immense economic power to be concentrated in a single corporation, as intervention to break the company up would violate the principle of non-interference, libertarian ideas may greatly diminish the liberty of the people subject to that corporate power. (shrink)

The authors find it more useful to payattention to relationships than to boundaries.By focusing attention on bounded, individualpsychological issues, the metaphor ofboundaries can distract helping professionalsfrom thinking about inequities of power. Itoversimplifies a complex issue, inviting us toignore discourses around gender, race, class,culture, and the like that support injustice,abuse, and exploitation. Making boundaries acentral metaphor for ethical practice can keepus from critically examining the effects ofdistance, withdrawal, and non-participation.The authors describe how it is possible toexamine the practical, moral, and ethicaleffects (...) of our participation in relationshipsby focusing on just relationships rather thanon boundaries. They give illustrations andclinical examples of relationally-focusedethical practices that derive from a narrativeapproach to therapy. (shrink)

In the early 1970s, the major industrial states were preparing to shift to nuclear fission as their principal source of electrical power. But that change has not occurred. In part, this is due to a growing public recognition that techniques and institutions for management of spent nuclear fuel, separated plutonium, and long-lived radioactive wastes are not yet fully developed. The consequent pressures for resolution have spurred a series of often ill-defined and sometimes contradictory attempts to promote international cooperation and (...) control of hazardous activities. How are these varied suggestions to be compared and evaluated? By what criteria can plans be selected that are likely to be both effective and negotiable? In this study, Gene I. Rochlin, physicist and social scientist, explores the technical, political, and institutional aspects of international nuclear export and fuel cycle policies. He categorizes existing proposals and suggests way to develop new ones that better promote both national and international goals. Dr. Rochlin argues neither for nor against the use of nuclear power or plutonium fuels. Instead, he addresses the question of how international arrangements could be reached that might jointly satisfy the objective of the several key nations, yet not be too difficult to negotiate. He concludes that a major fault has been the tendency to improvise arrangements for specific technical or industrial operations. As a result, overall social and political goals have become the bargaining points for compromise. Yet attempts to simultaneously resolve all problems are unlikely to prove fruitful. Dr. Rochlin suggests instead the formation of institutions organized around more limited social, political, and technical objectives, even at the expense of excluding some nations or omitting some aspects of the nuclear fuel cycle. Only by so doing, he argues, can immediate agreements be reached that preserve the potential for more comprehensive future arrangements without sacrificing industrial, environmental, or nonproliferation goals. This important book will be of interest to scientists, social scientists, government officials, and others concerned with the problems of plutonium management and nuclear wastes. (shrink)

Informed by a search of the literature about the usage of genetic testing information (GTI) by insurance companies, this paper presents a practical ethical analysis of several distinct public policy options that might be used to govern or constrain GTI usage by insurance providers. As medical research advances and the extension to the Human Genome Project (2016, https://en.wikipedia.org/wiki/human_genome_project_-_write) moves to its fullness over the next decade, such research efforts will allow the full synthesis of human DNA to be connected to (...) predictive health dispositions. As testing costs fall, there will be ever more pressure for citizens to disclose GTI. Genetic testing information is integral to future medical care because it can be used to better assess individually tailored medical therapies as well as to allow a more informed risk analysis by the insurance industry, which in some countries such as the USA underwrites a majority of citizen medical expenses. As discussed in this examination, the revelation of people’s uniquely personal GTI to insurers has enormous societal implications. The major contribution of the paper is to offer policy makers and concerned citizens a nuanced articulation of the basic options to regulate GTI, with a special consideration for ethical fairness and equity. As genetic-based medicine blossoms and pressures to reduce healthcare costs increase, there will be an ever greater impetus for countries to revisit their genetic testing policies. Organizations and policy makers striving to create GTI oversights perceived to be both “fair and effective” need to be aware of the ethical perspectives discussed in this paper. (shrink)

The cases for and against somatic gene therapy, germ-line gene therapy and gene therapy for enhancement are assessed. It is argued that none of these kinds of therapy is inherently wrong, and that an adequate assessment should consist in weighing risks and benefits. On this basis, it is argued that somatic therapy is a promising new kind of treatment that we should welcome; that we have technologies available that make germ-line therapy (...) superfluous, unless we want to engage in enhancement engineering; and that although we should be extremely cautious if we were to engage in enhancement engineering, we cannot categorically rule out that there might be cases in which this kind of therapy should be applied, e.g. if it was the only way of saving millions of lives. (shrink)

In light of the development of “CRISPR” technology, new promising advances in therapeutic and preventive approaches have become a reality. However, with it came many ethical challenges. The most recent worldwide condemnation of the first use of CRISPR to genetically modify a human embryo is the latest example of ethically questionable use of this new and emerging field. Monotheistic religions are very conservative about such changes to the human genome and can be considered an interference with God’s creation. Moreover, these (...) changes could cause perpetual changes to future generations. The Muslim scholars establish their decisions by addressing five foundations of Islamic law i.e. “maqāṣid al sharı̄`a”; the purposes of the law. These are dın̄, nafs, nasl, `aql and māl. To achieve this, the five principles should all be met before approval of an experiment like the Chinese embryo modifications; Qaṣd which is achieved in this case as it aims to protect the embryo from HIV. Yaqın̄ and Ḍarar were not satisfied as they require strong scientific certainty of the procedures, and evidence of safety. Ḍarūra by which the alternatives being compared; in this case more established and proven safe alternatives to protect the HIV transmission from the father are available, so this principle is not met. The final principle is `Urf, by which the social context of using any contemporary technology should be taken in consideration, and clearly this was not achieved. Collectively, germline changes are rejected from an Islamic perspective until the five principles are fulfilled. In the Chinese Twins gene editing case, there was clearly no justification or support for it according to the Muslim Jurisprudence laws. These laws and approaches can serve as an ethical checklist for such controversial research, especially in early stages of the research. (shrink)

Early last year, the GenEthics Consortium (GEC) of the Washington Metropolitan Area convened at George Washington University to consider a complex case about genetic testing for Alzheimer disease (AD). The GEC consists of scientists, bioethicists, lawyers, genetic counselors, and consumers from a variety of institutions and affiliations. Four of the 8 co-authors of this paper delivered presentations on the case. Supplemented by additional ethical and legal observations, these presentations form the basis for the following discussion.

In lieu of an abstract, here is a brief excerpt of the content:Reviewed by:Mimesis: Culture, Art, SocietyGene FendtMimesis: Culture, Art, Society, by Gunter Gebauer and Christoph Wulf; translated by Don Reneau; 400 pp. Berkeley: University of California Press, 1995, $45.00 cloth, $18.00 paper.The purpose of this book is to develop “a historical reconstruction of important phases in the development of mimesis” (p. 1) from a brief discussion of its pre-Platonic Greek significance through contemporary thinkers. It is, then, not strictly a (...) philosophical text, as are most of the texts and authors the book takes up. It is, however, a significant effort in the history of ideas, and as such it is shot through with traces of the traditional tropes, shaping power, ideology, and even social relations of that discipline, particularly as it is practiced in the venerable school of German scholarship. That is, the structure, tone, and argument of the book are shaped mimetically. This book’s problematic is, then, not simply historical, as Republic’s problem with the poets is not simply philosophical. Rather, both books partake of mimesis, even while each one aims to criticize or set forth the concept’s historical development.Let this stand as notice of a deep philosophical problem with the method of historical criticism. In fairness we should note that the authors are not unconscious of their difficulty here: “The fact that mimesis cannot be represented without the use of mimetic processes poses the fundamental problem of theory formation in reference to our object. What is the relation between the representational and the represented world? Is the representation of representation structurally equivalent to simple representation?” (p. 21). The authors hope to moot the power of those questions, if not the questions themselves, by attending “first of all to representations of mimesis found in texts best selected for that purpose and only afterward begin to offer considerations of a more generalizing nature” (p. 21). Their reasoning and choice of texts here is the traditional trope of the discipline: a mimema. Among other things, this methodos requires that the authors treat Girard as developing a “literary critical examination of [mimesis in] nineteenth and twentieth century novels” (p. 359n1) and a “new ordering of nineteenth century social relations” (p. 235), rather than, as he claims, a comprehensive anthropological thesis. At least, this method requires treating the former as essential, and the latter as less justifiable, for if Girard’s anthropological thesis about mimesis were justifiable a history of the idea of mimesis would be merely a heresiology. This problem can be restated mutatis mutandis for such thinkers as Plato and Augustine, whose theses—if they have theses—about mimesis are deeply anthropological.Two further questions arise early on and remain at the end. If, as the authors hold (and show), “the concept of mimesis necessarily loses its intellectual centrality with the rise of rational thought,” so much so that “the field of art, which comes to be regarded in the process as autonomous, undergoes a complete and fundamental restructuring” (p. 3), must we not begin to [End Page 199] suspect—as recent philosophers like Derrida attempt to show—that there is a dialectical relationship between the intentional, truth-functional relations of modern rational thought and the mimetic, unformalizable and “ambivalent” (pp. 2–3) processes of mimesis? Rather than conclude that “the question what is mimesis? is one which demonstratively leads to error” (p. 309), does it not begin to seem that intentional representation, as most visible in science, and mimetic assimilations, as most obviously effective in art, are together the necessary dialectical elements of culture, art and science? While it seems that the rise of rational scientific thought pushes mimesis to the social fringes of the arts, isn’t scientific activity and writing still just as much subject, and just as much a product, of the power of mimesis as art? Similarly art is just as bound as science to “probability” or “the convincing impossibility,” to recall Aristotle. This idea is not entirely foreign to the book; it appears subliminally as a plausible explication of the work of theorists like Benjamin and Adorno (pp. 267–93).The third difficulty is a question about selection. As in Auerbach’s renowned precursor, Wulf... (shrink)

C.S. Lewis was a major public intellectual in Britain, beginning from the late 1930s and continuing to his death in 1963. In both his non-fiction, especially The Abolition of Man, and his fiction, most importantly in That Hideous Strength, he offers a critique of rationalism and scientism that is often strikingly similar to those that Michael Oakeshott penned in the late 1940s and early 1950s. This essay examines the question to what extent this similarity is merely superficial, and to (...) what extent the two writers shared a similar basis for their views. Furthermore, it examines whether there is an actual thread of influence: had Oakeshott been reading Lewis before writing his critique of rationalism, and if so, to what extent did Lewis’s work inform Oakeshott’s? (shrink)

A close examination of Kim's argument in "Multiple Realization and the Metaphysics of Reduction" for the claim that if a kind is multiply realizable in a way that blocks identification with more fundamental properties it is also a kind unlikely to appear as an appropriate kind in a theory in the first place. Ultimately, I argue that there is one reasonably promising argument of this sort, but its success turns on explanatory questions the answers to which are far from obvious.

There is much we do not know about nanotechnology. Despite its tremendous promise, nanotechnology today is mostly forecast and fervent hope. Predictions that spending on nanotechnology will increase from current levels of $13 billion to more than $1 trillion by 2015 are no more than that – simply predictions. Hopes that nanotechnology will be an essential part of solving the globe's energy, food, and water problems should be tempered by recalling a century of revolutionary technologies that failed to live up (...) to their early promise such as nuclear energy, supersonic airplanes, or gene therapy. Many other questions continue to nip at nanotechnology's heels, not the least of which are debates about what is and is not technically feasible. Despite these uncertainties, we can have complete confidence in one aspect of nanotechnology's future – it will be subject to a host of regulations. (shrink)

Gene replacement therapy holds great promise in the treatment of many genetic CNS disorders. This commentary discusses the feasibility of gene replacement therapy in the unique context of the retina, with regard to: (1) the genetics of retinal neoplasia and degeneration, (2) available gene transfer technology, and (3) potential gene delivery vehicles.

Little is known about study co-ordinators of gene therapy clinical trials. The purposes of this study were to: (1) describe characteristics of co-ordinators of gene therapy (transfer) clinical trials; (2) assess differences between nurse and non-nurse study co-ordinators; and (3) identify factors indicative of study co-ordinators' role preparation that could affect their role performance. This exploratory correlational study employed a convenience sample of 118 co-ordinators in the USA (55 participants; 47% response rate). The researcher created the (...) Study Coordinator Role Preparedness and Performance Survey to assess factors or correlates of study co-ordinator performance. Analysis of variance was used to compare nurses and non-nurses, and men versus women on their perceived preparedness, perceived quality of orientation, and satisfaction with educational opportunities. The findings contribute to knowledge by identifying present inadequacies in the training of study co-ordinators and in recognizing the need for more effective provision of orientation and continuing education with respect to ethical issues, knowledge of genetic science, and potential research integrity challenges. (shrink)

The Streptococcus pyogenes CRISPR‐Cas system has gained widespread application as a genome editing and gene regulation tool as simultaneous cellular delivery of the Cas9 protein and guide RNAs enables recognition of specific DNA sequences. The recent discovery that Cas9 can also bind and cleave RNA in an RNA‐programmable manner indicates the potential utility of this system as a universal nucleic acid‐recognition technology. RNA‐targeted Cas9 (RCas9) could allow identification and manipulation of RNA substrates in live cells, empowering the study of (...) cellular gene expression, and could ultimately spawn patient‐ and disease‐specific diagnostic and therapeutic tools. Here we describe the development of RCas9 and compare it to previous methods for RNA targeting, including engineered RNA‐binding proteins and other types of CRISPR‐Cas systems. We discuss potential uses ranging from live imaging of transcriptional dynamics to patient‐specific therapies and applications in synthetic biology. (shrink)

The use of socially learned information (culture) is central to human adaptations. We investigate the hypothesis that the process of cultural evolution has played an active, leading role in the evolution of genes. Culture normally evolves more rapidly than genes, creating novel environments that expose genes to new selective pressures. Many human genes that have been shown to be under recent or current selection are changing as a result of new environments created by cultural innovations. Some changed in response to (...) the development of agricultural subsistence systems in the Early and Middle Holocene. Alleles coding for adaptations to diets rich in plant starch (e.g., amylase copy number) and to epidemic diseases evolved as human populations expanded (e.g., sickle cell and G6PD defi- ciency alleles that provide protection against malaria). Large-scale scans using patterns of linkage disequilibrium to detect recent selection suggest that many more genes evolved in response to agriculture. Genetic change in response to the novel social environment of contemporary modern societies is also likely to be occurring. The functional effects of most of the alleles under selection during the last 10,000 years are currently unknown. Also unknown is the role of paleoenvironmental change in regulating the tempo of hominin evolution. Although the full extent of culture-driven gene-culture coevolution is thus far unknown for the deeper history of the human lineage, theory and some evidence suggest that such effects were profound. Genomic methods promise to have a major impact on our understanding of gene-culture coevolution over the span of hominin evolutionary history. (shrink)

The article combines a criticism of public understanding of science with the sociology of expectations to examine how particular expectations toward scientific progress have performative effects for the construction of publics as citizens of science. By analyzing a particular controversy about gene therapy in Denmark, the article demonstrates how different sets of expectations can be used to discriminate among three different assemblages: the assemblage of consumption, the assemblage of comportment, and the assemblage of heroic action. Each of these (...) assemblages makes medical science, scientific citizenship, politics, patients, doctors, and expectations toward the future emerge in particular ways. By their radically different expectations toward science and their different constructions of what it means to be a scientific citizen, the assemblages construct the objectives of the governance of science in three very different ways. (shrink)

Cancer drugs are broadly classified into two categories: cytotoxic chemotherapies and targeted therapies that specifically modulate the activity of one or more proteins involved in cancer. Major advances have been achieved in targeted cancer therapies in the past few decades, which is ascribed to the increasing understanding of molecular mechanisms for cancer initiation and progression. Consequently, monoclonal antibodies and small molecules have been developed to interfere with a specific molecular oncogenic target. Targeting gain‐of‐function mutations, in general, has been productive. However, (...) it has been a major challenge to use standard pharmacologic approaches to target loss‐of‐function mutations of tumor suppressor genes. Novel approaches, including synthetic lethality and collateral vulnerability screens, are now being developed to target gene defects in p53, PTEN, and BRCA1/2. Here, we review and summarize the recent findings in cancer genomics, drug development, and molecular cancer biology, which show promise in targeting tumor suppressors in cancer therapeutics. (shrink)

Gene therapy is the modification of the human genetic code to prevent disease or cure illness. This technology is in its infancy and remains confined to experimental clinical trials. Once the present barriers are overcome, gene therapy will confront humanity with a host of ethical challenges. Therapies targeted to the genes of germ-line cells will introduce permanent changes to the human gene pool. Furthermore, nonmedical gene modifications have the potential to introduce a new form (...) of eugenics into our society by which some members attempt to become inherently superior to others and humanity is re-engineered to man-made specifications. National Catholic Bioethics Quarterly 10.1 (Spring 2010): 45–50. (shrink)

Spinal muscular atrophy (SMA) is the most common genetic disease that causes infant mortality. Its treatment and prevention represent the paradigmatic example of the ethical dilemmas of 21st‐century medicine. New therapies (nusinersen and AVXS‐101) hold the promise of being able to treat, but not cure, the condition. Alternatively, genomic analysis could identify carriers, and carriers could be offered in vitro fertilization and preimplantation genetic diagnosis. In the future, gene editing could prevent the condition at the embryonic stage. How should (...) these different options be evaluated and compared within a health system? In this paper, we discuss the ethical considerations that bear on the question of how to prioritize the different treatments and preventive options for SMA, at a policy level. We argue that despite the tremendous value of what we call ‘ex‐post’ approaches to treating SMA (such as using pharmacological agents or gene therapy), there is a moral imperative to pursue ‘ex‐ante’ interventions (such as carrier screening in combination with prenatal testing and preimplantation genetic diagnosis, or gene editing) to reduce the incidence of SMA. There are moral reasons relating to autonomy, beneficence and justice to prioritize ex‐ante methods over ex‐post methods. (shrink)

In March 1996, the General Accounting Office (GAO) issued the reportScientific Research: Continued Vigilance Critical to Protecting Human Subjects.It stated that “an inherent conflict of interest exists when physician-researchers include their patients in research protocols. If the physicians do not clearly distinguish between research and treatment in their attempt to inform subjects, the possible benefits of a study can be overemphasized and the risks minimized.” The report also acknowledged that “the line between research and treatment is not always cleartoclinicians. Controversy (...) exists regarding whether certain medical procedures should be categorized as research.”This problem currently plagues gene transfer research. A few months prior to the GAO report, an ad hoc committee appointed by National Institutes of Health (NIH) Director Harold Varmus expressed similar concerns in its assessment of NIH investment in research on gene therapy. (shrink)

In March 1996, the General Accounting Office (GAO) issued the reportScientific Research: Continued Vigilance Critical to Protecting Human Subjects.It stated that “an inherent conflict of interest exists when physician-researchers include their patients in research protocols. If the physicians do not clearly distinguish between research and treatment in their attempt to inform subjects, the possible benefits of a study can be overemphasized and the risks minimized.” The report also acknowledged that “the line between research and treatment is not always cleartoclinicians. Controversy (...) exists regarding whether certain medical procedures should be categorized as research.”This problem currently plagues gene transfer research. A few months prior to the GAO report, an ad hoc committee appointed by National Institutes of Health (NIH) Director Harold Varmus expressed similar concerns in its assessment of NIH investment in research on gene therapy. (shrink)

In March 1996, the General Accounting Office issued the report Scientific Research: Continued Vigilance Critical to Protecting Human Subjects. It stated that “an inherent conflict of interest exists when physician-researchers include their patients in research protocols. If the physicians do not clearly distinguish between research and treatment in their attempt to inform subjects, the possible benefits of a study can be overemphasized and the risks minimized.” The report also acknowledged that “the line between research and treatment is not always clear (...) to clinicians. Controversy exists regarding whether certain medical procedures should be categorized as research.”This problem currently plagues gene transfer research. A few months prior to the GAO report, an ad hoc committee appointed by National Institutes of Health Director Harold Varmus expressed similar concerns in its assessment of NIH investment in research on gene therapy. (shrink)

Comprising eight revised essays and seven new pieces, this work provides a comprehensive resource for students, scientists, bioethicists, physicians, and laypeople to better understand and discuss the ethical issues underlying this technology that has the potential to forever change the world.

This article presents evidence supporting the claim that ethical reasoning is a skill that can be taught and assessed. We propose a working definition of ethical reasoning as 1) the ability to identify, analyze, and weigh moral aspects of a particular situation, and 2) to make decisions that are informed and warranted by the moral investigation. The evidence consists of a description of an ethical reasoning education program—Ethical Reasoning in Action —designed to increase ethical reasoning skills in a variety of (...) situations and areas of life. ERiA is housed at a public, major comprehensive U.S. university—James Madison University—and assessment of the program focuses on interventions delivered prior to and during orientation for incoming first-year students. Findings indicate that the interventions measurably enhance the ability of undergraduate students to reason ethically. ERiA’s competency-targeted program and positive student learning outcomes offers a promising model for higher education ethics programs seeking to connect classroom learning in ethics to decision-making in everyday life. (shrink)

As a philosopher interested in biomedical ethics, I find recent advances in genetic technologies both fascinating and frightening. Future technologies for genetic therapies and elimination of clearly deleterious genes offer us the ability to get rid of the cause of much human suffering, seemingly at its physiological root. But memories of past eugenics programs gone horribly awry must make cautious our initial optimism for these generally well-intentioned programs. Most often the scientist proceeds in research with the best of intentions, but (...) that does not make all scientific investigation worth pursuing. (shrink)

Genetic diseases can be every bit as devastating as the diseases caused by bacteria or viruses, and in one way they are much worse: we pass them on to our children, generation after generation after generation. Science and medicine have provided us with clues to the treatment of a few genetic diseases, although by their very nature they have never been considered curable. But, as William R. Clark shows, that is about to change through one of the most profound revolutions (...) in modern medicine: gene therapy, a branch of the new field of molecular medicine. The New Healers is a clear and compelling introduction to a revolution in modern medicine that may lead to cures for cancer, AIDS, and nearly 4,000 previously incurable genetic diseases. Clark introduces us to the scientists working on the vast Human Genome Project, and outlines all the basic elements of molecular biology necessary to understand this remarkable new medicine. (shrink)

It can be argued that there is an ethical requirement to classify correctly what is known and what is unknown in decision situations, especially in the context of biomedicine when risks and benefits have to be assessed. This is because other methods for assessing potential harms and benefits, decision logics and/or ethical principles may apply depending on the kind or degree of uncertainty. However, it is necessary to identify and describe the various epistemic states of uncertainty relevant to such estimates (...) in the first place. Therefore, this paper aims to develop a category system of different epistemic states of uncertainty which, although not exclusively, is primarily intended to be applied to early clinical trials. It is formed on the basis—and various combinations—of three dimensions of uncertainty that represent certain parts of incomplete knowledge: outcome (type of event), probability (of outcome) and evaluation (assessment of outcome). Furthermore, it is argued that uncertainty can arise from three different sources (the structure of the object of research, the state of the evidence, or individual handling of the research and already existing knowledge). The categories developed are applied to actual examples from gene therapy and genome editing to illustrate that they can be helpful for a more precise definition of the respective uncertainties, especially in the context of risk–benefit assessment. The categories allow a differentiated perspective of decision-making situations from the point of view of incomplete knowledge in general, but particularly, for example, in early clinical research, and may thereby support a more acceptable ethical assessment of potential harms and benefits. (shrink)

CRISPR is currently viewed as the central tool for future gene therapy. Yet, many prominent scientists and bioethicists have expressed ethical concerns around CRISPR gene therapy. This paper provides a critical review of concerns about CRISPR gene therapy as expressed in the mainstream academic literature, paired with replies also generally found in that literature. The expressed concerns can be categorised into three types depending on whether they stress risk/benefit ratio, autonomy and informed consent, or (...) concerns related to various aspects of justice. In the reviewed literature, we found no intrinsic objections to CRISPR gene therapy, even though many such objections were present in discussions of gene editing in the 1990s. The paper then proposes a brief outline for a practically applicable moral framework for public decision-making about CRISPR gene therapy and suggests how such a framework might be supported. We also suggest that this framework should govern public engagement about CRISPR gene therapy in order to reduce the risk that we make decisions about CRISPR gene therapy based on misperceptions, inflated views of risk, or unreasonable moral or religious views. (shrink)