Most patients suffering from progressive dementia have thoughts, emotions, perspectives, and perceptions of a world of experience. Decisions about life‐sustaining treatment should incorporate a principled approach to evaluating what life is like for these patients.

In lieu of an abstract, here is a brief excerpt of the content:Demystifying the Mystery of Alzheimer's as Late, No Longer Mild Cognitive ImpairmentPeter J. Whitehouse (bio)Keywordsaging, Alzheimer’s disease, deconstruction, mild cognitive impairmentProfessor Tom Kirkwood and Michael Bavidge's comments are welcome additions to our discourse as both emphasize the importance of considering mild cognitive impairment (MCI) and Alzheimer's disease (AD) in relationship to the normal biological and cultural processes of aging. Whereas I agree with my colleague and co-author, Atwood (...) Gaines' response, I wish to add my own commentary to update the reader concerning the dynamic political processes at work in the social construction and deconstruction of MCI and AD. I have referred to MCI as autodeconstructing AD because whatever we come to think of the MCI label on the spectrum of cognitive aging should alter our beliefs about the ultimate utility of the concept of AD. Tensions in the field of study of MCI have increased since the project reported in this journal began. The social science and philosophical contributions toward understanding MCI need to inform our debate now; otherwise, we will be less effective at influencing a critical debate for society about its relationships to medicine, science, and modern capitalism.This past year, Ron Petersen, the major proponent of the concept of MCI was awarded the prestigious Potamkin Prize for research in Alzheimer's disease by the American Academy of Neurology. The National Institute on Aging (NIA) placed the discovery of MCI as first on the list of contributions during twenty years of research funded through hundreds of millions of dollars poured into the NIA Alzheimer's Research Centers. Some have even suggested that we relabel MCI of the amnestic type, Petersen syndrome. Yet, John Morris, who was co-awarded the Potamkin Prize, has continued to write that MCI is early AD and most recently has suggested (Morris 2006) that we should revise our diagnostic criteria. He joins me and a growing list of other so-called thought leaders who believe (but do not always state publicly) that the term MCI is not useful clinically. Lon Schneider (2005) has recently joined the camp of critics publicly by suggesting that MCI is [End Page 87] not only confusing clinically but is now possibly retarding research.The proliferation of different kinds of MCI indicates that we are studying heterogeneous processes of brain aging. Whereas, John Morris suggests that we relabel MCI as early AD, I have suggested the converse. For example, in a grand rounds lecture at Johns Hopkins in March 2004, I used the lecture title "LNLMCI (late no longer MCI)" as a synonym for AD.Kirkwood is right to compare the quest for biological therapy for AD to the search to treat aging processes in other organs. He has been an outspoken critic of anti-aging medicine quackery that claims that aging itself is a disease that can be reversed today. But, if AD is brain aging, are we not in fact creating a "disease" category that raises false hopes and expectations?Kirkwood also points out that aging is a lifespan process. To prevent dementia in older individuals, we should prevent damage to neurons in younger individuals. Recently, it has been claimed, for example, that exposure to lead in young animals makes these animals more at risk for amyloid deposition in later life (Basha et al. 2005). Whether or not lead directly affects the pathogenesis of AD, it seems eminently reasonable to try to prevent damage to neurons in young children so that they may have maximum cognitive capacity throughout their lifespan.Almost ten years ago, when I stepped down as the editor of the Alzheimer's Disease and Associated Disorders Journal and as John Morris took over this responsibility, I wrote an editorial calling for the end of AD (Whitehouse 2001). In other words, I argued that thinking through the invention of the term mild cognitive impairment reveals that we are attempting to assign medical categories to what are a heterogeneous set of processes that affect our brains as we age. At the hundredth anniversary of the first case of what we have come to call Alzheimer's disease, perhaps it is time to reflect on the individual and social... (shrink)

Community discourse about the moral status of animals is critical to the future of bioethics and, indeed, to the future of modern society. Thomasma and Loewy are to be commended for sharing thoughts and trying to attain some common ground. I am grateful to them for fostering discussion and allowing me to respond. I cannot endorse the negative tone of the end of their conversation, however. They end with serious concerns about the possibility of any agreement between themselves. Even though (...) I perceive some moral differences between them, I do not believe that they are moral strangers. In this commentary I review the ways in which I agree and disagree with Thomasma and Loewy and conclude with some thoughts about the kind of broad ethical thinking we need to do to address our moral relationship to nonhuman, living creatures. (shrink)

Van Rensselaer Potter was the first voice to utter the word “bioethics,” yet he is too little appreciated by the bioethics community. My expectations for my first visit with Professor Van Rensselaer Potter were primed by conversations with leaders and historians of the field of biomedical ethics, including Warren Reich, Al Jonsen, and David Thomasma. When mentioning my interest in environmental ethics and my concerns for the current state of biomedical ethics, I was told that I must meet Van. On (...) my first visit to Madison, Wisconsin, Van met me at the McArdle Laboratories for Cancer Research at the University of Wisconsin, where he spent essentially his entire academic career as a basic oncological researcher. He was dressed informally and driving a rusting1984 Subaru station wagon with a license plate that read YES ZPG. We spent this first portion of our visit at the Institute where he is an Emeritus Professor and has contributed to understanding cancer metabolism as recognized by his election to the National Academy of Sciences. However, Van felt most at home in his shack located outside Madison. This country retreat included a rather primitive hut surrounded by acres of property owned by the family. I felt at the heart of Van's world when I sat in one of a pair of inexpensive plastic outdoor chairs in a particularly secluded part of the woods on the property, the place where Van himself communed with nature. (shrink)

As science learns more about how the brain works, and fails to work, the possibility for developing “cognition enhancers” becomes more plausible. And the demand for drugs that can help us think faster, remember more, and focus more keenly has already been demonstrated by the market success of drugs like Ritalin, which tames the attention span, and Prozac, which ups the competitive edge. The new drug Aricept, which improves memory, most likely will join them. Whether such drugs are good for (...) individuals, or for society, is an open question, one that demands far more public discussion. (shrink)

In this paper, we suggest some of the dimensions of the problematic concept of Alzheimer Disease as a natural disease discerned by increasingly sophisticated medical scientific progress. Taking a page from Max Weber concerning unique events, we show some of the conceptual building blocks and social processes that have coalesced into the perception of certain phenomena as abnormalities that are seen as implicated in the development of a degenerative disease distinct from the process of normal, but variable, brain aging. We (...) note some of the decisions and social forces pushing for particular conceptualizations, interpretations, and reifications of brain alterations. In so doing, we suggest that the mystery of the "there" may not be much different from, and probably is, the mystery of the "everywhere". (shrink)

Over the last century, Alzheimer’s disease has proven a highly malleable concept. Initially an obscure diagnosis pertaining to rare cases of young onset dementia, by the latter half of the 20th cen...

In all facets of our lives, humans construct meaning to understand their place in the world and their relationships to one another and to broader environments. Within this semantic web, words, stor...

Book reviewed in this article: To Do No Harm: DES and the Dilemmas of Modern Medicine. By Roberta J. Apfel and Susan M. Fisher.

Book reviewed in this article: To Do No Harm: DES and the Dilemmas of Modern Medicine. By Roberta J. Apfel and Susan M. Fisher.

Pharmaceutical companies are major sponsors of biomedical research. Most scholars and policymakers focus their attention on government and academic oversight activities, however. In this article, I consider the role of pharmaceutical companies’ internal ethics statements in guiding decisions about corporate research and development (R&D). I review materials from drug company websites and contributions from the business and medical ethics literature that address ethical responsibilities of businesses in general and pharmaceutical companies in particular. I discuss positive and negative uses of pharmaceutical (...) companies’ ethics materials and describe shortcomings in the companies’ existing ethics programs. To guide employees and reassure outsiders, companies must add rigor, independence, and transparency to their R&D ethics programs. (shrink)

Biological ontologies are used to organize, curate, and interpret the vast quantities of data arising from biological experiments. While this works well when using a single ontology, integrating multiple ontologies can be problematic, as they are developed independently, which can lead to incompatibilities. The Open Biological and Biomedical Ontologies Foundry was created to address this by facilitating the development, harmonization, application, and sharing of ontologies, guided by a set of overarching principles. One challenge in reaching these goals was that the (...) OBO principles were not originally encoded in a precise fashion, and interpretation was subjective. Here we show how we have addressed this by formally encoding the OBO principles as operational rules and implementing a suite of automated validation checks and a dashboard for objectively evaluating each ontology’s compliance with each principle. This entailed a substantial effort to curate metadata across all ontologies and to coordinate with individual stakeholders. We have applied these checks across the full OBO suite of ontologies, revealing areas where individual ontologies require changes to conform to our principles. Our work demonstrates how a sizable federated community can be organized and evaluated on objective criteria that help improve overall quality and interoperability, which is vital for the sustenance of the OBO project and towards the overall goals of making data FAIR. Competing Interest StatementThe authors have declared no competing interest. (shrink)

For over 50 years, since the development of nuclear-armed ICBMs, the USA has sought a way to defend against them. These efforts evolved through various strategies and technologies: from nuclear-tipped rockets through space-based laser weapons to today’s system of ground-based kinetic-kill interceptors. Public debate around these issues reached a peak in the 1980s with President Reagan’s Strategic Defense Initiative, popularly known as Star Wars.Rebecca Slayton examines this history in Arguments that Count, a valuable and well-told account of a particular (...) aspect of missile defense: computer software. Missile defense required identifying a hostile missile launch, keeping track of thousands of incoming warheads on their ballistic trajectories, and directing interceptors to the right place—and doing all this in less than 30 minutes. From the outset, designers turned to computers to do the complex calculations quickly enough. But missile defense presented an additional factor, in that any m .. (shrink)

Arguments over the value of ‘extreme music’ and the use of highly controversial imagery within these genres have existed since its inception. Detractors claim that using extreme imagery such as fascist symbols, pornography and racially charged photographs inherently promotes the corrosive ideologies behind these images. Some purveyors of extreme music disagree, arguing that musicians use these images to explore humanity’s darker elements which, in turn, allow audiences to better understand these problematic aspects of modern society. When played out within underground (...) music communities, these arguments often devolve into name calling and accusations of censorship. However, by addressing extreme music on its own terms and critiquing the effectiveness of these genres, a more nuanced understanding of the issues intrinsically embedded within extreme music emerges. In this article, I employ this approach by exploring the music and imagery of power electronics band Whitehouse and argue that the ambiguous nature of their work partially mirrors the intention behind Paulo Freire’s concept of codifications. While this notion provides some defence for extreme music more broadly, the lack of venues that promote communal explorations of these images hinders the genre’s ability to achieve its own goals. (shrink)

"Patient advocates can help make research more ethical, but advocacy raises ethical issues of its own.

Lynne Rudder Baker, Saving Belief: A Critique of Physicalism Princeton: Princeton University Press, 1987, xii + 177 pp. Daniel C. Dennett, The Intentional Stance Cambridge: MIT Press, 1987, xi + 388 pp. Paul M. Churchland, Matter and Consciousness Cambridge: MIT Press, revised edition, 1988, xii + 184 pp.

Research using human embryonic stem cells raises an array of complex ethical issues, including, but by no means limited to, the moral status of developing human life. Unfortunately much of the public discussion fails to take into account this complexity. Advocacy for liberal and conservative positions on human embryonic stem cell research can be simplistic and misleading. Ethical concepts such as truth-telling, scientific integrity, and social justice should be part of the debate over federal support for human embryonic stem cell (...) research. Moreover, the debate should be conducted in accord with principles of deliberative democracy, including respect for people holding competing views. (shrink)

Acknowledgments 1. Culture Is Essential 2. Culture Exists 3. Culture Evolves 4. Culture Is an Adaptation 5. Culture Is Maladaptive 6. Culture and Genes Coevolve 7. Nothing about Culture Makes Sense except in the Light of Evolution.

The norm of assertion, to be in force, is a social norm. What is the content of our social norm of assertion? Various linguistic arguments purport to show that to assert is to represent oneself as knowing. But to represent oneself as knowing does not entail that assertion is governed by a knowledge norm. At best these linguistic arguments provide indirect support for a knowledge norm. Furthermore, there are alternative, non-normative explanations for the linguistic data (as in recent work from (...) Van Elswyk). Direct arguments would rely on normative judgments about the permissibility or impermissibility of assertions with and without the speaker knowing the content asserted. John Turri's work experimental results purport to show that our norm of assertion is factive, and probably knowledge. But as a number of recent experimentalists (Kneer, Reuter and Broessel, Marsili and Wiegmann) have shown, Turri's results rely on the problemmatic use of 'should' as in 'Maria should assert that she owns a 1990 watch.' Correcting for this, these experimentalists provide strong evidence that our norm of assertion is not factive. The standard reply to evidence like this from the assertion of unlucky falsehoods is the excuse maneuver. But Marsili and Wiegmann, following Turri's protocol for testing for excuse validation, show that participants who judge that assertions unlucky falsehoods are permissible are not guilty of excuse validation. Given our current understanding of the experimental evidence, knowledge is not our norm of assertion. (shrink)

What is the biological function of perception? I hold perception, especially visual perception in humans, has the biological function of accurately representing the environment. Tyler Burge argues this cannot be so in Origins of Objectivity (Oxford, 2010), for accuracy is a semantical relationship and not, as such, a practical matter. Burge also provides a supporting example. I rebut the argument and the example. Accuracy is sometimes also a practical matter if accuracy partly explains how perception contributes to survival and reproduction.

Authorising euthanasia and assisted suicide with advance euthanasia directives is permitted, yet debated, in the Netherlands. We focus on a recent controversial case in which a Dutch woman with Alzheimer’s disease was euthanised based on her AED. A Dutch euthanasia review committee found that the physician performing the euthanasia failed to follow due care requirements for euthanasia and assisted suicide. This case is notable because it is the first case to trigger a criminal investigation since the 2002 Dutch euthanasia law (...) was enacted. Thus far, only brief descriptions of the case have been reported in English language journals and media. We provide a detailed description of the case, review the main challenges of preparing and applying AEDs for persons with dementia and briefly assess the adequacy of the current oversight system governing AEDs. (shrink)

When patients have progressive and incurable dementia, should their advance directives always be followed? Contra Dworkin, Dresser argues that when patients remain able to enjoy and participate in their lives, directives to hasten death should sometimes be disregarded.

This paper argues for the general proper functionalist view that epistemic warrant consists in the normal functioning of the belief-forming process when the process has forming true beliefs reliably as an etiological function. Such a process is reliable in normal conditions when functioning normally. This paper applies this view to so-called testimony-based beliefs. It argues that when a hearer forms a comprehension-based belief that P (a belief based on taking another to have asserted that P) through the exercise of a (...) reliable competence to comprehend and filter assertive speech acts, then the hearer's belief is prima facie warranted. The paper discusses the psychology of comprehension, the function of assertion, and the evolution of filtering mechanisms, especially coherence checking. (shrink)

Progress Unchained reinterprets the history of the idea of progress using parallels between evolutionary biology and changing views of human history. Early concepts of progress in both areas saw it as the ascent of a linear scale of development toward a final goal. The 'chain of being' defined a hierarchy of living things with humans at the head, while social thinkers interpreted history as a development toward a final paradise or utopia. Darwinism reconfigured biological progress as a 'tree of life' (...) with multiple lines of advance not necessarily leading to humans, each driven by the rare innovations that generate entirely new functions. Popular writers such as H. G. Wells used a similar model to depict human progress, with competing technological innovations producing ever-more rapid changes in society. Bowler shows that as the idea of progress has become open-ended and unpredictable, a variety of alternative futures have been imagined. (shrink)

The revised Common Rule adopts the reasonable person standard to guide research disclosure. Some members of the research community contend that the standard is confusing and ill-suited to the research oversight system. Yet the revised rule is not as radical as it might seem. During the 1970s, judges started using the standard to evaluate negligence claims brought by injured patients who said doctors had failed to obtain informed consent to the harmful procedures. In its influential Belmont Report, the National Commission (...) recommended application of a “reasonable volunteer standard” to guide IRBs evaluating research disclosures. Evidence also suggests that IRBs often invoke the reasonable person standard in deliberations about consent forms. But past application of the standard has been informal and uneven. Robust application of the reasonable person standard will require researchers and IRBs to learn more about what ordinary people want and need to know about the studies they are invited to join. Input from people with personal experience as study participants could be particularly useful to this effort. (shrink)