Mutations in DNA topoisomerase II are often correlated with drug‐resistance in tumor cell lines. Studies of topoisomerase II‐mediated drug‐resistance in various model systems, as well as the sequencing of such mutations from drug‐resistant tumors, have shed light on the functional domains of topoisomerase II, on how it interacts with inhibitors, and on the different mechanisms by which cells avoid the toxic effects of many clinically important anti‐tumor drugs.

Genomic research results and incidental findings with health implications for a research participant are of potential interest not only to the participant, but also to the participant's family. Yet investigators lack guidance on return of results to relatives, including after the participant's death. In this paper, a national working group offers consensus analysis and recommendations, including an ethical framework to guide investigators in managing this challenging issue, before and after the participant's death.

Human genomics is a translational field spanning research, clinical care, public health, and direct-to-consumer testing. However, law differs across these domains on issues including liability, consent, promoting quality of analysis and interpretation, and safeguarding privacy. Genomic activities crossing domains can thus encounter confusion and conflicts among these approaches. This paper suggests how to resolve these conflicts while protecting the rights and interests of individuals sequenced. Translational genomics requires this more translational approach to law.

This collection of essays examines how philosophers in the Western tradition have viewed and written about children through the ages. (Philosophy).

The current explosion of genetic knowledge and the rapid proliferation of genetic tests has rightly provoked concern that we are approaching a future in which people will be labeled and disadvantaged based on genetic information. Indeed, some have already suffered harm, including denial of health insurance. This concern has prompted an outpouring of analysis. Yet almost all of it approaches the problem of genetic disadvantage under the rubric of “genetic discrimination.”This rubric is woefully inadequate to the task at hand. It (...) ignores years of commentary on race and gender demonstrating the limits of antidiscrimination analysis as an analytic framework and corrective tool. Too much discussion of genetic disadvantage proceeds as if scholars of race and gender had not spent decades critiquing and developing antidiscrimination theory.Indeed, there are multiple links among race, gender, and genetics. Dorothy Roberts has discussed the historical links between racism and genetics, while she and others have begun to map connections between gender and genetics. (shrink)

"Reasonably priced and beautifully produced. A clear and helpful introduction by Susan Okin, one of the leading feminist scholars of our generation, as well as a useful bibliography and chronology of Mill's life.... Invaluable for teaching and scholarship alike." --Ian Shapiro, Yale University.

Participant-driven research is a burgeoning domain of research innovation, often facilitated by mobile technologies. Return of results and data are common hallmarks, grounded in transparency and data democracy. PDR has much to teach traditional research about these practices and successful engagement. Recommendations calling for new state laws governing research with mHealth modalities common in PDR and federal creation of review mechanisms, threaten to stifle valuable participant-driven innovation, including in return of results.

Oversight of human gene transfer research presents an important model with potential application to oversight of nanobiology research on human participants. Gene therapy oversight adds centralized federal review at the National Institutes of Health's Office of Biotechnology Activities and its Recombinant DNA Advisory Committee to standard oversight of human subjects research at the researcher's institution and at the federal level by the Office for Human Research Protections. The Food and Drug Administration's Center for Biologics Evaluation and Research oversees human gene (...) transfer research in parallel, including approval of protocols and regulation of products. This article traces the evolution of this dual oversight system; describes how the system is already addressing nanobiotechnology in gene transfer: evaluates gene therapy oversight based on public opinion, the literature, and preliminary expert elicitation; and offers lessons of the gene therapy oversight experience for oversight of nanobiotechnology. (shrink)

Returning genomic research results to family members raises complex questions. Genomic research on life-limiting conditions such as cancer, and research involving storage and reanalysis of data and specimens long into the future, makes these questions pressing. This author group, funded by an NIH grant, published consensus recommendations presenting a framework. This follow-up paper offers concrete guidance and tools for implementation. The group collected and analyzed relevant documents and guidance, including tools from the Clinical Sequencing Exploratory Research Consortium. The authors then (...) negotiated a consensus toolkit of processes and documents. That toolkit offers sample consent and notification documents plus decision flow-charts to address return of results to family of living and deceased participants, in adult and pediatric research. Core concerns are eliciting participant preferences on sharing results with family and on choice of a representative to make decisions about sharing after participant death. (shrink)

Successful preimplantation genetic diagnosis to avoid creating a child affected by a genetically-based disorder was reported in 1989. Since then PGD has been used to biopsy and analyze embryos created through in viuo fertilization to avoid transferring to the mother’s uterus an embryo affected by a mutation or chromosomal abnormality associated with serious illness. PGD to avoid serious and early-onset illness in the child-to-be is widely accepted. PGD prevents gestation of an affected embryo and reduces the chance that the parents (...) will be faced with a difficult decision of whether to terminate the pregnancy. More controversial have been PGD to select the sex of the child-to-be for “family balancing”, PGD for mere susceptibility to disease and for late-onset disorders such as Alzheimer diseas, and most controversially, PGD to create a donor child who is Human Leukocyte Antigen (HLA-matched with a preexisting sibling in need of stem cell transplant. (shrink)

Technology has outpaced the capacity of researchers performing research on human participants to interpret all data generated and handle those data responsibly. This poses a critical challenge to existing rules governing human subjects research. The technologies used in research to generate images, scans, and data can now produce so much information that there is significant potential for incidental findings, findings generated in the course of research but beyond the aims of the study. Neuroimaging scans may visualize the entire brain and (...) even the entire head; computed tomography colonography research may visualize the entire torso, from the base of the lungs to the pubis; genetics studies may reveal “extra” and sometimes unwanted information about the family, such as misattributed paternity and undisclosed adoption; and genomic microarray research increasingly involves whole-genome analysis revealing an individual’s complete genotype, with enormous potential for uncovering unexpected information about an individual’s genetics and risks of developing future conditions. (shrink)

The problem of incidental findings in human subjects research—findings of potential health importance to the research participant that the researcher stumbles upon while pursuing the aims of the research—may at first seem of minor significance. The number and potential gravity of incidental findings force researchers to face difficult questions. The most fundamental of these is whether researchers have any duty to identify, evaluate, and disclose these findings to the research participant. This is a profound challenge to the structure of bioethics (...) and health law. Both fields approach the world of research and the world of medical care very differently. Neuroimaging research can yield a high number of incidental findings. Bioethics and health law must now reconstitute the traditional vision of researcher duties to bring the researcher back into a relationship with the research participant. (shrink)

The Moral Economies of American Authorship argues that the moral character of authors became a kind of literary property within mid-nineteenth-century America's expanding print marketplace, shaping the construction, promotion, and reception of texts as well as of literary reputations.

The Covid‐19 pandemic has exposed four myths in bioethics. First, the flood of bioethics publications on how to allocate scarce resources in crisis conditions has assumed authorities would declare the onset of crisis standards of care, yet few have done so. This leaves guidelines in limbo and patients unprotected. Second, the pandemic's realities have exploded traditional boundaries between clinical, research, and public health ethics, requiring bioethics to face the interdigitation of learning, doing, and allocating. Third, without empirical research, the success (...) or failure of ethics guidelines remains unknown, demonstrating that crafting ethics guidance is only the start. And fourth, the pandemic's glaring health inequities require new commitment to learn from communities facing extraordinary challenges. Without that new learning, bioethics methods cannot succeed. The pandemic is a wake‐up call, and bioethics must rise to the challenge. (shrink)

Museums and collecting is now a major area of cultural studies. This selected group of key texts opens the investigation and appreciation of museum history. Edward Edwards, chief pioneer of municipal public libraries, chronicles the founders and early donors to the British Museum. Greenwood and Murray provide informative pictures of the early history of the museum movement. Sir William Flower, Director of the British Museum (Natural History), takes a pioneering philosophical approach to the sphere of natural history in relation to (...) museums. Similarly, Acland and Ruskin discuss and explore the relationships of art and architecture to museums. (shrink)

Genetic testing poses fundamental questions for insurance. Testing can predict a low probability of future illness and disability, which can help promote the insurability of individuals with a family history of genetic risk, but it can also invite insurers to reject applicants, increase premiums, exclude people with certain illnesses and disabilities, and otherwise adjust the underwriting processes for individuals with certain genotypes. In the workplace, these issues may cause employers who offer or pay for insurance to alter their hiring behavior, (...) either by selecting those with desirable genetic makeup or rejecting, dismissing, or reassigning those who carry an unwanted risk, ultimately threatening employability and the safety net that insurance is intended to provide. (shrink)

Both bioethics and law have governed human genomics by distinguishing research from clinical practice. Yet the rise of translational genomics now makes this traditional dichotomy inadequate. This paper pioneers a new approach to the ethics of translational genomics. It maps the full range of ethical approaches needed, proposes a “layered” approach to determining the ethics framework for projects combining research and clinical care, and clarifies the key role that return of results can play in advancing translation.

A Skeptical View of the Liberal Peace reflects on the place of democracy in the global community. The article pays particular attention to the widespread assumption that there is an inherent relationship between democracy and peace, and that peace most assuredly is derived from democracy itself. I find these assertions to be highly questionable and overstated. Reflection on the philosophy which underpins these claims can only be helpful for international relations. In particular, given the United States’ apparent imperialistic urge to (...) force democracies on other nations as Iraq, the article seems especially timely. (shrink)

Moral debate over vegetarianism forms the backdrop to a preliminary consideration of the questions: Is it ethical to produce, sell and eat faux meat? Is it ethical to produce, sell and wear fake animal skin? Is it ethical to sell or wear secondhand or thriftshop genuine animal skin? If vegetarianism is morally required, the question of just what uses of nonhuman animals are ethical or unethical and on what grounds is always on tap. In this piece, I examine the above (...) questions in light of deontological then utilitarian reasons for vegetarianism. I conclude deontological or animal rights grounds entail the moral condemnation of faux meat and fake and secondhand animal skin. I conclude utilitarian or animal welfare grounds entail, with some qualification, the moral acceptability of faux meat and fake animal skin but the clear moral unacceptability of secondhand animal skin. (shrink)

Developing ethical standards for clinical use of large-scale genome and exome sequencing has proven challenging, in part due to the inevitability of incidental or secondary findings. Policy of the American College of Medical Genetics and Genomics has evolved but remains problematic. In 2013, ACMG issued policy recommending mandatory analysis of 56 extra genes whenever sequencing was ordered for any indication, in order to ascertain positive findings in pathogenic and actionable genes. Widespread objection yielded a 2014 amendment allowing patients to opt-out (...) from analysis of the extra genes. In 2015, ACMG published the amended policy, providing that patients could opt out of the full set of extra genes, but not a subset. In 2016, ACMG enlarged the set and indicated planned expansion of the roster of extra genes to include pharmacogenetic findings. ACMG policy does not protect the respect for patient choice that prevails in other domains of clinical medicine, where informed consent allows patients to opt in to desired testing. By creating an expanding domain of genomic testing that will be routinely conducted unless patients reject the entire set of extra tests, ACMG creates an exceptional domain clinical practice that is not supported by ethics or science. (shrink)

Charles V was a scholarly king who commissioned French versions of ancient & medieval treatises for the express purpose of guiding his government. To translate Aristotle's "Politics" he chose Nicole Oresme, an ingenious philosopher whose aptitude & attitudes made him an effective supporter of the Valois monarchy. Oresme's task was to take his text out of the language of a small but international community of scholars & adapt it to serve the French people, making it accessible to a new & (...) broad audience. Contents: Oresme & his Version of the "Politics"; Oresme & the Commentary Tradition of the "Politics"; Nat. Sovereignty & the Hierarchy of Communities; The Public State & the Common Good; The "Politics," the "Livre de Politiques," & the Church; Aristotle, Oresme, & Gallicanism; Conclusion; & Bibliography. (shrink)

This piece explores the proposition that environmental restoration is the only acceptable alternative to a world left with diminishing natural regions. The article reviews the ethical debate concerning the moral obligation of humankind to restore regions that have been stripped of their resources. It demonstrates thatthrough the assistance of both legislative and technological measures nature can be renewed to spawn healthy ecosystems when permitted to do so. Furthermore, the article claims that the restoration thesis is proven by the paradigm of (...) the Adirondack region – a region that was once clear-cut and enabled to restore itself through both rewilding and the “Forever Wild” clause in the New York State Constitution. The article is particularly timely and provocative given the current Bush Administration’s environmental policies. (shrink)

_Hegel or Spinoza_ is the first English-language translation of the modern classic _Hegel ou Spinoza._ Published in French in 1979, it has been widely influential, particularly in the work of the philosophers Alain Badiou, Antonio Negri, and Gilles Deleuze. _Hegel or Spinoza_ is a surgically precise interrogation of the points of misreading of Spinoza by Hegel. Pierre Macherey explains the necessity of Hegel’s misreading in the kernel of thought that is “indigestible” for Hegel, which makes the Spinozist system move in (...) a way that Hegel cannot grasp. In doing so, Macherey exposes the limited and situated truth of Hegel’s perspective—which reveals more about Hegel himself than about his object of analysis. Against Hegel’s characterization of Spinoza’s work as immobile, Macherey offers a lively alternative that upsets the accepted historical progression of philosophical knowledge. He finds in Spinoza an immanent philosophy that is not subordinated to the guarantee of an a priori truth. Not simply authorizing a particular reading—a “good” Spinoza against a “bad” Hegel—_Hegel or Spinoza_ initiates an encounter that produces a new understanding, a common truth that emerges in the interval that separates the two. (shrink)

No consensus yet exists on how to handle incidental fnd-ings in human subjects research. Yet empirical studies document IFs in a wide range of research studies, where IFs are fndings beyond the aims of the study that are of potential health or reproductive importance to the individual research participant. This paper reports recommendations of a two-year project group funded by NIH to study how to manage IFs in genetic and genomic research, as well as imaging research. We conclude that researchers (...) have an obligation to address the possibility of discovering IFs in their protocol and communications with the IRB, and in their consent forms and communications with research participants. Researchers should establish a pathway for handling IFs and communicate that to the IRB and research participants. We recommend a pathway and categorize IFs into those that must be disclosed to research participants, those that may be disclosed, and those that should not be disclosed. (shrink)