Hirschsprung disease and the multiple endocrine neoplasia type 2 syndromes are hereditary disorders related to the abnormal migration, proliferation or survival of neural crest cells and their derivatives. Hirschsprung disease is a frequent disorder of the enteric nervous system, resulting in intestinal obstruction. The multiple endocrine neoplasia type 2 syndromes predispose to cancers of neural crest derivatives. Both diseases are associated with heterozygous mutations in the RET proto‐oncogene. RET encodes a transmembrane receptor tyrosine kinase expressed in neural crest lineages and (...) whose ligand, glial‐cell‐line‐derived neurotrophic factor, has been very recently identified. In vitro expression studies demonstrate that while Hirschsprung disease mutations result in loss of function of the mutant RET tyrosine kinase, multiple endocrine neoplasia type 2 mutations lead to its constitutive activation. Thus, the two ‘faces’ of RET, gain of function and loss of function, each lead to a different syndrome, respectively: multiple endocrine neoplasia type 2, a cancer syndrome, or Hirschsprung disease, a developmental defect. (shrink)

Some years ago a collection of historical and philosophical essays on sex was advertised under the slogan: Philosophers are interested in sex again. Since that time the history of sexuality has become an almost unexceptionable topic, occasioning as many books and articles as anyone would ever care to read. Yet there are still fundamental conceptual problems that get passed over imperceptibly when this topic is discussed, passed over, at least in part, because they seem so basic or obvious that it (...) would be time badly spent to worry too much about them. However, without backtracking toweard this set of problems, one will quite literally not know what one is writing the history of when one writes a history of sexuality.An excellent example of some of the most sophisticated current writing in this field can be found in Western Sexuality, a collection of essays that resulted from a seminar conducted by Philippe Ariès at the Ecole des Hautes Etudes en Sciences Sociales in 1979-80.1 As one would expect, Western Sexuality is characterized by a diversity of methodological and historiographical approaches—social history, intellectual history, cultural history , historical sociology, the analysis of literary texts, and that distinctive kind of history practiced by Michel Foucault and also in evidence in the short essay by Paul Veyne. One perspective virtually absent from this collection is the history of science, and since I believe that the history of science has a decisive and irreducible contribution to make to the history of sexuality, it is not accident that I am going to focus on that connection. But the history of sexuality is also an area in which one’s historiography or implicit epistemology will stamp, virtually irrevocably, one’s first-order historical writing. It is an arena in which philosophical and historical concerns inevitably run into one another. 1. Philippe Ariès and Adnré Béjin, eds., Western Sexuality: Practice and Percept in Past and Present Times . Arnold I. Davidson, a coeditor of Critical Inquiry, is assistant professor of philosophy and member of the Committees on General Studies in the Humanities and on the Conceptual Foundations of Science at the University of Chicago. His previous contribution to Critical Inquiry, “How to Do the History of Psychoanalysis: A Reading of Freud’s Three Essays on the Theory of Sexuality,” appeared in the Winter 1987 issue. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Back to the Future:Obtaining Organs from Non-Heart-Beating CadaversRobert M. Arnold (bio) and Stuart J. Youngner (bio)Organ Transplantation requires viable donor organs. This simple fact has become the Achilles' heel of transplantation programs. Progress in immunology and transplant surgery has outstripped the supply of available organs. Between 1988 and 1991, for example, the number of transplant candidates on waiting lists increased by about 55 percent, while the number of (...) donors increased only about 16 percent.1 By the end of March 1993, more than 30,000 potential recipients awaited transplantation (United Network for Organ Sharing Database (UNOS) 1993). Every day six of these patients die prior to receiving a heart or liver transplant, while patients needing kidney transplants must tolerate a lower quality of life on dialysis (Grenvik 1992; Evans, Orians, and Ascher 1992).This scarcity is likely to get worse. As transplantation becomes more successful, it is being offered to sicker and older patients. Attempts to transplant other solid organs, such as small bowel and pancreas, will only fuel the demand for donors. However, the current source of organs is unlikely to grow. Most organs come from patients who have been declared dead by neurologic criteria (commonly referred to as "brain dead" or heart-beating cadaver donors (HBCDs) because their hearts are beating at the time of procurement). Estimates of the potential pool of HBCDs have been revised downward from 20,000-27,000 to roughly 10,000-12,000 (Nathan et al. 1991). Improvements in automobile safety and handgun legislation will likely lead to further reductions. Moreover, the rate of procurement from HBCDs has remained relatively flat despite extensive public awareness campaigns and legislation requiring hospitals to routinely request donation from families of dead patients (Caplan et al. 1992).If organ transplantation is going to continue to flourish, alternative [End Page 103] sources of organs must be found. Recently the University of Pittsburgh Medical Center (UPMC) proposed procuring organs from patients who have been declared dead by traditional cardiopulmonary rather than brain-oriented criteria after they or their families have decided to forgo life-sustaining treatment—hereafter referred to as the Pittsburgh protocol (UPMC Policy 1993). These patients are typically referred to as non-heart-beating cadaver donors (NHBCDs) because their hearts are no longer beating at the time of organ procurement.Although NHBCDs were a major source of transplantable kidneys prior to the institution of death by neurologic criteria, their usefulness was limited by "warm ischemia time." This term refers to the injury to tissues that occurs when the blood supply is interrupted and before the organs are cooled and reperfused. Under the Pittsburgh protocol, therapy is withdrawn in the operating room where a waiting surgical team removes organs immediately after death is declared. By controlling the place and time of death, it has been possible to minimize warm ischemia time and thus solve the technical problems previously associated with procurement from NHBCDs.The potential contribution of NHBCD organs is significant. Nathan (1992), using data from Delaware Valley Transplant Program, concludes that the use of severely brain injured, but not "brain dead" patients, would increase the donor pool by 20-25 percent. Moreover, unpublished data from the Pittsburgh organ procurement organization, the Center for Organ Recovery and Education (CORE), suggests that these organs, particularly kidneys, function as well as those procured from HBCDs (Broznick 1993).This volume is devoted to the ethical, psychosocial, and public policy implications of procuring organs from non-heart-beating cadaver donors after a discussion to forgo life-sustaining treatment. The genesis of this volume was a project in which we invited leading experts in transplantation, ethics, and public policy to use the Pittsburgh protocol as a starting point for exploring a broad range of issues associated with attempts to procure organs from NHBCDs. The issues raised by NHBCDs turned out to have important implications about the fundamental conceptual and moral assumptions underlying organ procurement.Although each of the papers in this volume can be read separately, we intend the volume to be read as a whole. Many of the latter pieces on the ethical implications of the policy are best understood in light of the earlier background papers... (shrink)

External reality is not moved by our personal dramas; even when our world is collapsing, the world continues its normal course, as if nothing had happened. Of course we know that the most poignant human suffering will not stop the sun from shining or the world from turning. Yet there are moments when the disharmony between objective reality and our own emotional state is painful and even surprising. It seems as if the world is provocatively uninterested in what is most (...) dear to us.The awareness of this rift is evoked in the first sentence of Borges’ well-known story translated into Dutch under the title De Aleph, "On the harrowing morning in February when Beatriz Viterbo died... I saw that the iron poster boards in the Plaza Constitución were being pasted over with some type of advertising for light cigarettes; this struck me, for I understood that the restless, enormous universe was already withdrawing from her, and that this was the first change in an endless series".What is the theoretical relevance of this experience, often roused by poetry and prose, but seldom discussed by philosophers? Is Borges referring to a purely subjective experience from which no conclusion can be drawn, or does he speak of an experience containing an important theoretical insight? Regardless, our ability to undergo this experience is evidently independent of our favourite philosophical concepts. Even someone who adheres to a theory that accepts a meaningful reality can experience this rift when he observes the sun shining triumphantly on a day of mourning. Similarly, someone having no metaphysical belief in a meaningful reality can remain immune to the type of rift Borges describes.Yet it cannot be denied that this rift experience is strengthened and legitimized by an important development in knowledge. The science has evoked a world view that strictly separates objective facts from subjective values. The reality presented by science, is not an inspired relationship or meaningful construction where humanity finds its place and from which it derives its dignity. Laws discovered by science say nothing of good or evil and contain no message on the meaning of life. Science is a source of trustworthy information not elevating, inspiring or comforting concepts. From a scientific viewpoint, knowledge of objective reality has nothing to do with insights people use to orient their lives.This separation of knowledge and wisdom contrasts sharply with a traditional view where knowledge of the most fundamental characteristics of reality also offers an insight in the meaning of human life. Nietzsche described this contrast as follows: while people have always tended to believe that what concerns them most also lies at the heart of reality, they must now realize that their moral, religious or aesthetic values merely form a superficial world of appearances; what elicits wonder or strong emotion is only a blossom on a reality that, in its deeper roots, is not at all beautiful or moving.The disenchantment brought on by science creates a breach or rift. Everything we experience as mysterious, enchanted or moving, appears also to exist as a reality coldly and neutrally described by science. Science demystified the rainbow that once appeared as a mysterious, divine phenomenon: what had always seemed wondrous can apparently be explained by the same natural laws that regulate the most banal or prosaic phenomena. (shrink)

The current debate about the moral status of animals is strongly determined by a misunderstanding of the role of moral intuitions. It is often assumed that our moral intuitions contain an implicit understanding of something that could ideally always be made explicit in terms of a consistent set of general principles. I have argued that this assumption is certainly wrong with respect to our moral intuitions about how we should behave towards animals. The meaning of these intuitions will always be (...) intimately tied up with deeply ingrained attitudes which precede the endorsement of any explicit moral view. While it cannot be excluded that these attitudes might radically change, it is wrong to suppose that such a transformation could result from abstract reasoning. (shrink)

Influential contemporary thinkers have declared that the belief in individual autonomy rests on an illusion. They have argued that our subjectivity is shaped by the language we speak and the traditions to which we belong. One should not, however, overestimate the impact of these theoretical criticisms. The idea of individual autonomy is part of a larger pattern of belief which has not ceased to exert its influence on our habits of thinking and behaving.The belief that we are fully autonomous subjects (...) is associated with the belief that we should identify ourselves with the detached, objectifying attitude which is an essential element of the scientific outlook. We like to believe that our real self is to be distinguished from any role we happen to fulfill or any position we happen to occupy. Instead of admitting that we are constituted in our deepest self by our commitments and allegiances, we would prefer to see these commitments and allegiances as the expressions of our individual desires and free decisions. The kind of individualism which is related to the idea of individual autonomy need not be amoral or egoistic, but it can easily be combined with a kind of moral universalism. A commitment to an abstract ideal is not incompatible with individual autonomy. (shrink)

When I was asked to formulate some questions or remarks about Prof. Barry’s paper, it was probably assumed that I would not confine myself to the expression of pure agreement. And yet, that is what I am inclined at first to do. I do agree that the view he criticizes is wrong for the reasons he mentions. And I admire the clarity and vigour of his arguments. However the reasons one has for agreeing with a thesis may belong to a (...) context that is very different from the context the thesis itself belongs to. Prof. Barry’s paper can be read at one level as the defence of a certain policy — it contains political recommendations. It is at that level that I entirely agree with it. But his recommendations are probably part of a theoretical outlook I do not share.The question I would like to deal with is: “How should the position which is the target of Brian Barry’s criticism be characterized?” One could say that it is anti-liberal. It is certainly opposed to the liberalism Brian Barry advocates. But there are, I think, also good reasons for characterizing it as a kind of liberalism. It is a sort of excessive, perverse, loony liberalism, but liberalism nevertheless. For the sake of convenience I call it quasi-liberalism. (shrink)

De tweespalt tussen wetenschap en emotionele waarneming werkt ontluisterend. Donder en Bliksem, de regenboog en andere als wonderbaarlijk ervaren natuurverschijnselen worden herleid tot fysieke fenomenen. Hoewel dit ook bevrijdend kan werken, blijft het verschil tussen realiteit en ons perceprievermogen een grote tweespalt genereren.

Some moral philosophers view conventional morality as an instrument that has a certain function to fulfill, and that we can in principle correct or adjust on the basis of an understanding of that function. This instrumentalist approach to morality is an extension of a familiar pattern of thought constituted by the combination of two different elements. We tend, on the one hand, to believe that we have a clear understanding of what it is that we allow ourselves to be guided (...) by when we are motivated by something moral. We identify this moral motivation with something that is, at first sight, transparent and unproblematic, viz. with some sort of altruism. The willingness to act morally is the willingness to be concerned with the happiness, welfare and interests of others.On the other hand, we are also familiar with the idea that traditional or conventional morality is a culturally dependent product of historical processes which have created in us certain beliefs and patterns of feeling and response. The moral judgments that we are inclined to make on the basis of unexamined intuitions owe their existence and appeal, at least partially, to a contingent cultural and historical context.The combination of these two elements leads to a familiar project: we should view whatever is contingent with a critical eye, by determining towhat extent it can be justified on the basis of insight into what is essential . Or to put in another way, we should check if the unexamined, intuitive judgments that we tend to pronounce actually agree with the explicitly formulated universal principles which we consciously endorse.An illustration of this way of thinking can be found in the current discussion about what might be called ‘moral proximity’. The extent to which we feel involved in the joys and sorrows of others depends, among other things, on how near they are to us. This proximity can be conceived in different ways: familiarity, kinship, proximity in space or time. We feel greater sympathy towards our friends or acquaintances than towards people we have never met and about whom we know very little. The suffering of disaster victims in our own country affects us more deeply than the fate of those who experienced the same thing in some distant country. The tragedies of many centuries ago do not horrify us now, and we cannot easily get worked up over the fate of future generations. (shrink)

Two perspectives on religion are contrasted. From the internalist perspective religion is not in need of any neutral justification: its point is manifest within religious life itself, just as the point of morality is manifest within moral life. From the externalist perspective religious practices and attitudes are dependent on the truth of certain assumptions about supernatural realities. It is argued that there are good reasons for endorsing internalism and, consequently, for radically dissociating religion from belief: if religious discourse is non-literal (...) , belief becomes dispensable. Finally, however, it is admitted that the internalist, by drawing a sharp line between literal and non-literal language, might miss an important truth about religion. (shrink)

It is argued that the point of the ideal of human rights is to protect individuals against oppressive regimes or cruel traditions. This negative description should not be converted into a positive one: it would be wrong to speak in terms of human rights about whatever people need in order to have meaningful lives. The reason why many philosophers are tempted to make that wrong move is that two kinds of individualism are easily conflated. The thesis that individuals should not (...) be oppressed because of their choices or commitments is translated into the thesis that freedom of individual choice should be maximized. The ideal of individual autonomy which manifests itself in the latter thesis is also at the origin of the belief that our moral intuitions should be justified in terms of the principles we consciously and explicitely endorse. The author argues that this belief has implications which are unacceptable to anybody. (shrink)