Introduction. The inadequacy of the support measures provided to children with orphan diseases is exacerbated by the trend towards an increase in the number of children with such a diagnosis. Orphan diseases also include diseases caused by primary immunodeficiency or congenital errors of immunity, which are life-threatening. However, these people are part of society and require attention from it, and social and economic measures from the state. Most of them, with proper treatment, socialization and appropriate (...) government support, can lead a normal life and live a full life. Scientific novelty of the research. On the basis of the study results, the authors contribute to clarifying the principles used in the implementation of the security function of the social state. The targeting of social support measures must be supplemented with the principles of social justice and freedom to choose ways to meet the needs of specific categories of citizens, understood as follows. The welfare state supports those citizens who need it most of all, namely, the poor. Specific categories of citizens can satisfy their needs, while having the opportunity to choose. This opportunity arises thanks to the receipt of targeted assistance in the form of monthly or annual subsidies. Families with children with orphan diseases should also be included in these categories. If they have the right to receive annual government subsidies, they will be able to spend these funds depending on the current needs due to the state of health of their children with orphan diseases (for the purchase of socially important food products; medicines, medical nutrition, and various services). The aim of the work is to study the problems of providing support measures to children with orphan diseases in the context of the current model of the welfare state. The article analyzes the satisfaction of patients with congenital immunity errors with various types of state support, identifies problems that reduce their satisfaction. Methods. The authors use methods such as comparative analysis, study of regulatory legal acts, sociological analysis. Results. On the basis of the study results the effectiveness of measures of state support for children with orphan diseases, studying the best experience of foreign countries, proposals were made to clarify the principles used to implement the security function by the social state, to expand the composition of the subjects involved in providing support measures analyzed in the article. Conclusions. The results obtained make it possible to assert that the targeted approach, which is basic in the model of the welfare state, does not cover most of the problems of children with innate immunity errors and, accordingly, the families that represent their interests. (shrink)

BackgroundApproximately 7% of the general population is affected by an orphan disease, which, in the United States, is defined as affecting fewer than 1 in 1500 people. Disease awareness is often low and time-to-diagnosis delayed. Different legislations worldwide have created incentives for pharmaceutical companies to develop drugs for orphan diseases. A journalistic article in Bloomberg Businessweek has claimed that pharmaceutical companies have tried marketing orphan drugs by placing a specific disease into the popular television series “House, (...) M.D.” which features diagnostic journeys and was produced between 2004 and 2012. This study aimed to describe the presentation of orphan diseases in the television series “House, M.D.”, to test in an exploratory fashion the hypothesis that treatable orphan conditions are overrepresented in “House, M.D.” and to discuss whether such marketing practices may or may not be ethical.MethodsA list of all medical cases depicted in the television series “House, M.D.” was obtained and classified as orphan or non-orphan according to the Orphanet database. The ratios of orphan diseases among all diseases, such with an orphan drug designation and such with an orphan drug approval by the FDA were then compared with conservative approximations of real world conditions (chi-squared tests for equality of proportions). STROBE criteria were respected.ResultsOut of a total of n = 181 different medical diagnoses, n = 42 (23.2%) were orphan diseases. The difference in percentages in between “House, M.D.” and reality was not statistically significant for orphan diseases overall (p = 0.96), yet was statistically significantly higher for both orphan diseases with one or more orphan drug designations (p = 0.0192) and such with one or more approved orphan drugs (p < 0.0001).ConclusionsOrphan diseases with a designated and/or approved orphan drug were overrepresented in the television series “House, M.D.” with statistical significance while orphan diseases overall were not. This may be explained by (so far) undocumented efforts of pharmaceutical companies to place their orphan drugs in the television series, as described in the article in Bloomberg Businessweek. Further research is needed into marketing practices in popular and emerging media formats. (shrink)

The rule of rescue describes the moral impulse to save identifiable lives in immediate danger at any expense. Think of the extremes taken to rescue a small child who has fallen down a well, a woman pinned beneath the rubble of an earthquake, or a submarine crew trapped on the ocean floor. No effort is deemed too great. Yet should this same moral instinct to rescue, regardless of cost, be applied in the emergency room, the hospital, or the community clinic? (...) -/- In health care, the desire to save lives at any cost must be reconciled with the reality of resource scarcity. As one example, the estimated cost for prophylactic Factor VIII to treat one patient with hemophilia for one year is $300,000. Costs of this magnitude have been accepted by public and private insurers in the developed world, even though, in principle, these sums could provide greater overall health benefit if allocated to pay for the unmet health care needs of many other patients. Looking forward, however, broad application of the rule of rescue will be increasingly untenable. But the moral instinct will remain: the desire to help those weakest among us, especially when their small numbers allow us to see them as unique individuals. What, then, is the ethical framework that can guide coverage and reimbursement decisions for orphan drugs into the future? (shrink)

This essay outlines the moral dilemma of funding orphan drug research and development. To date, ethical aspects of priority setting for research funding have not been an issue of discussion in the bioethics debate. Conflicting moral obligations of beneficence and distributive justice appear to demand very different levels of funding for orphan drug research. The two types of orphan disease, rare diseases and tropical diseases, however, present very different ethical challenges to questions about allocation of (...) research funds. The dilemma is analysed considering utilitarian and rights based theories of justice and moral obligations of non-abandonment and a professional obligation to advance medical science. The limitations of standard economic evaluation tools and other priority setting tools used to inform health policy decision makers on research funding decisions are outlined. (shrink)

An urgent need for standards and guidelines on genetic testing has arisen because of swift advances in research, facilitated by the Human Genome Project. The goals of the Human Genome Project include the identification of all genes and sequencing of the human genome. The project is currently ahead of schedule and under budget. We can expect an avalanche of genetic information, much of which will be relevant to human disease. In addition to the Human Genome Project, investigator-initiated research projects and (...) commercial biotechnology laboratories are discovering human disease genes at a breathtaking pace. Technology transfer has been rapid and has led to the availability of numerous clinical tests within only a few years since the first disease gene yielded to the technique of positional cloning. Disease genes are selected for study for a number of reasons. Genes for rare diseases may be studied before more common disorders because they elucidate an important area of pathogenesis. Unfortunately, technology transfer to the clinic for rare tests is hindered by several factors. Standards need to be established to assure that genetic tests for rare diseases are not ignored or mismanaged in the rush to commercialize tests for more common human genetic diseases. (shrink)

The PRIME Institute of the College of Pharmacy, University of Minnesota, recently released preliminary research findings indicating a trend of extraordinary pharmaceutical industry pricing of drug products in the United States (U.S.). According to researchers at the PRIME Institute, such extraordinary price increases are defined as any price increase that is equal to, or greater than, 100% at a single point in time. In some instances, PRIME Institute researchers found that drugs exhibiting extraordinary price increases are categorized as "orphan (...) drugs" (or blood-related biologic treatments) and often life-saving or life-sustaining for treating the cause or symptoms of diseases affecting fewer than 200,000 people in the U.S., or where there is prevalence of less than 5 per 10,000 people afflicted with a disease or symptoms in the community. Because of extraordinary price increases for orphan drugs — some exceeding 1000% at a single point in time -this article addresses two interrelated questions: Are extraordinary orphan drug price increases socially responsible behavior? If so, are the pharmaceutical industry's policies providing orphan drug access to American consumers in dire need of available life-sustaining and life-enhancing pharmaceuticals considered "socially responsible" behavior? The author concludes, after an interdisciplinary analysis of the legal, economic, sociopolitical, and ethical dimensions of orphan drug pricing, that they are not socially responsible – unless justified by cost and availability of health care marketplace/patient options. Furthermore, the author recommends a socially responsible industry strategic approach to insure that patients ultimately receive -regardless of cost -timely access to life-saving and life-sustaining orphan drugs. (shrink)

With the human genome mapped, and with the mapping of more than one hundred animal genomes in progress, the amount of genetic data available is increasing exponentially. This exponential increase in data is having an immediate impact on the process of drug development. By using techniques of information technology to manipulate data regarding the genes, proteins, and biochemical pathways associated with various diseases, scientists are beginning to be able to design drugs in a systematic fashion. In the context of (...) any given disease, scientists look to see whether a gene, a protein for which the gene codes, or another protein in the relevant biochemical pathway could be the “target” biological molecule, the “knocking out” of which would halt or slow the disease's progression. Once a target molecule has been identified and characterized structurally, drug therapies that would be likely to knock out this target can be identified and tested systematically. The merger of information technology and genetic technology has changed the process of pharmaceutical development so much that a new term—bioinformatics—has been coined to describe this new approach to such development. (shrink)

Orphan drug policy often gives ‘special treatment’ to rare diseases, by giving additional priority or making exceptions to specific drugs, based on the rarity of the conditions they aim to treat. This essay argues that the goal of orphan drug policy should be to make prevalence irrelevant to funding decisions. It aims to demonstrate that it is severity, not prevalence, which drives our judgments that important claims are being overlooked when treatments for severe rare diseases are (...) not funded. It shows that prioritising severity avoids problems caused by prioritising rarity, and that it is compatible with a range of normative frameworks. The implications of a severity-based view for drug development are then derived. The severity-based view also accounts for what is wrong with how the current system of drug development unfairly neglects common diseases that burden the developing world. Lastly, the implications of a severity-based view for current orphan drug policies are discussed. There are no data in this work. (shrink)

Rare diseases are a heterogenic group of disorders with a little in common except of their rarity affecting by less than 5 : 10.000 people. In the world is registered about 6000-8000 rare diseases with 6-8% suffering population only in the European Union. In spite of rarity, they represent an important medical and social problem due to their incidence. For many rare diseases have no treatment, but if it exists and if started on time as being available (...) to patients, there is a good prognosis for them to be able for normal life. The problems of patients affected by rare diseases are related to the lack of diagnosis and timely undergoing as well as their treatment or prevention. Orphan drugs are products intended for treatment, diagnosis or prevention of rare diseases, but for their development and marketing the industry has not been interested in yet because of their marketing reasons. Patients suffering from a rare disease although belonging to the vulnerable group for their specific health needs, is becoming invisible in the health care system due to their additional needs un properly recognized. Ethical problems faced by patients, but also health care professionals are related to the allocation of medical diagnostics, unequal approach to health care, inappropriately specialized social services as well as therapy and rare orphan drugs unavailability. Ethical questions related to clinical trails on orphan drugs, population screening and epidemiology testing on rare diseases will also be discussed in this paper. [Projekat Ministarstva nauke Republike Srbije, br. 41004: Rare diseases: Molecular pathophysiology, the diagnostic and therapeutical modalities, social, ethical and legal aspects] Retke bolesti su veoma heterogena grupa poremecaja i imaju malo toga zajednickog osim retkosti, posto pogadjaju manje od pet osoba na 10.000 ljudi. U svetu je evidentirano izmedju 6.000 i 8.000 retkih bolesti koje pogadjaju sest do osam procenata stanovnistva samo u Evropskoj uniji. Dakle, iako retke, one predstavljaju vazan medicinski i socijalni problem s obzirom na broj obolelih. Za mnoge retke bolesti nema terapije, a ukoliko ona postoji i ako se na vreme zapocne i bude dostupna pacijentima, postoje dobri izgledi da ce oboleli moci da zive normalnim zivotom. Problemi s kojima se susrecu pacijenti sa retkim bolestima vezani su za dijagnostikovanje u smislu nemogucnosti ili nepravovremenog postavljanja dijagnoze, kao i same terapije ili prevencije pojave bolesti. Orphan lekovi su proizvodi koji su namenjeni za lecenje, dijagnozu ili prevenciju retkih bolesti, za ciji razvoj i marketing industrija nije zainteresovana iz trzisnih razloga. Pacijenti s retkim bolestima, iako pripadaju osetljivoj grupi, jer imaju specificne zdravstvene potrebe, ostaju nevidljivi u zdravstvenom sistemu, jer se njihove dodatne specificne potrebe ne prepoznaju. Eticki problemi s kojima se susrecu pacijenti, ali i zdravstveni radnici, ticu se alokacije zdravstvene dijagnostike, nejednakog pristupa zdravstvenoj zastiti i nezi, nedostatka specijalizovanih socijalnih usluga, kao i nepostojanja i nedostupnosti terapije orphan lekovima. Eticka pitanja retkih klinickih ispitivanja orphan lekova i populacionih i skrining ispitivanja u vezi sa retkim bolestima takodje su razmatrani u ovom radu. PR Projekat Ministarstva nauke Republike Srbije, br. 41004: Rare diseases: Molecular pathophysiology, the diagnostic and therapeutical modalities, social, ethical and legal aspects. (shrink)

For a significant number of patients, there exists no, or only little, interest in developing a treatment for their disease or condition. Especially with regard to rare diseases, the lack of commercial interest in drug development is a burning issue. Several interventions have been made in the regulatory field in order to address the commercial disinterest in these conditions. However, existing regulations mainly focus on the provision of incentives to the sponsors of clinical trials of orphan drugs, and (...) leave unanswered the overarching question about the rightful place of orphan drugs in resource allocation systems. In this article, we analyse the ethical aspects of funding research and development in the field of rare diseases. We then propose an ethical framework that can help health policy makers move forward in the difficult matter of fairly allocating resources for the prevention, diagnosis and treatment of rare diseases. (shrink)

This article is about the justifiability of accepting worse cost effectiveness for orphan drugs, that is, treatments for rare diseases, in a publicly financed health care system. Recently, three arguments have been presented that may be used in favour of exceptionally advantageous economic terms for orphan drugs. These arguments share the common feature of all referring to considerations of justice or fairness: the argument of the irrelevance of group size, the argument from the principle of need, and (...) the argument of identifiability. It is argued that all of these arguments fail to support the conclusion that orphan drugs should be subsidized to a larger extent than treatments for common diseases. The argument of the irrelevance fails to distinguish between directly and indirectly relevant considerations of fairness or justice. The recent attempt to revive the moral relevance of identifiability has provided no novel reasons to think that identifiability is morally relevant in itself or due to considerations of fairness and justice. The argument from the principle of need does not fail due to any inherent flaw in the principle as such. Rather, this principle can be interpreted in different ways, and none of these interpretations support exceptionally advantageous terms economically for treating rare diseases specifically. It is concluded that we are awaiting justice based reasons for the preferential treatment of orphan drugs. (shrink)

It is hard to argue with the proposition that value for money should guide health spending. However, even after decades of development, economic evaluation is still a work in progress. As applied, it deals poorly with issues of social justice, ageing and end of life issues; cases involving small numbers—such as decisions about orphan drugs—are also contested. Unfortunately, differences in incremental cost-effectiveness ratios are presented with a degree of precision which contributes to an ‘illusion of validity’.1 Nobel Laureate Amartya (...) Sen has suggested that ‘when all the requirements of ubiquitous market-centred evaluation have been incorporated into the procedures of cost–benefit analysis, it is not so much a discipline as a daydream’.2 As with any approach to public decision making, the use of economic evaluation rests on an implicit social licence, including that the decision making is fair and reasonable. Many countries have developed special policies for rare, ‘ultrarare’ or ‘orphan’ diseases to moderate the effect of a ubiquitous application of economic evaluation. The threshold for defining ‘small’ or rare is a matter of judgement and ranges between 2 and 80 per 100 000 population.3 Magalhaes challenges the ethical basis of special programmes for low incidence conditions and argues against such provisions. In this commentary, I will argue the contrary: that there are good reasons …. (shrink)

In recent years, the biopharmaceutical industry has seen an increase in the development of so-called orphan drugs for the treatment of rare and neglected diseases. This increase has been spurred on by legislation in the United States, Europe, and elsewhere designed to promote orphan drug development. In this article, we examine the drivers of corporate social responsibility (CSR) activities in orphan drug markets and the extent to which biopharmaceutical firms engage in these activities with a strategic (...) orientation. The unique context of orphan drugs constitutes a research opportunity to test the applicability of existing theoretical perspectives on CSR and strategic CSR. Using Schwartz and Carroll’s (Bus Ethics Q, 13(4):503–530, 2003) three-domain approach to CSR and the literature on strategic CSR as a theoretical background, we employ a combination of semi-structured interviews and a quantitative website content analysis to study practices of biopharmaceutical firms in the United States and European Union. Our findings show that both US- and EU-based companies engaged in orphan drugs development perceive their involvement as a responsible business activity beyond the economic dimension of CSR. However, for the majority of these companies their CSR activities do not qualify as strategic according to the criteria established in the literature. We also find significant differences between larger and smaller firms in their use of CSR. Based on these findings, we make several suggestions regarding orphan drug legislation and other measures that might help firms exploit strategic CSR benefits. (shrink)

Next SectionEvidence based medicine is rightly at the core of current medicine. If patients and society put trust in medical professional competency, and on the basis of that competency delegate all kinds of responsibilities to the medical profession, medical professionals had better make sure their competency is state of the art medical science. What goes for the ethics of clinical trials goes for the ethics of medicine as a whole: anything that is scientifically doubtful is, other things being equal, ethically (...) unacceptable. This particularly applies to so called orphaned fields of medicine, those areas where medical research is weak and diverse, where financial incentives are lacking, and where the evidence regarding the aetiology and treatment of disease is much less clear than in laboratory and hospital based medicine. Examples of such orphaned fields are physiotherapy, psychotherapy, medical psychology, and occupational health, which investigate complex syndromes such as RSI, whiplash, chronic low back pain, and chronic fatigue syndrome. It appears that the primary ethical problem in this context is the lack of attention to the orphaned fields. Although we agree that this issue deserves more attention as a matter of potential injustice, we want to argue that, in order to do justice to the interplay of heterogeneous factors that is so typical of the orphaned fields, other ethical models than justice are required. We propose the coordination model as a window through which to view the important ethical issues which relate to the communication and interaction of scientists, health care workers, and patients. (shrink)

Mucopolysaccharidosis VI is an autosomal recessive lysosomal storage disorder associated with severe disability and premature death. The presence of a mucopolysaccharidosis-like disease in indigenous ethnic groups in Colombia can be inferred from archaeological findings. There are several indigenous patients with mucopolysaccharidosis VI currently receiving enzyme replacement therapy. We discuss the ethical and economic considerations, regarding both direct and indirect costs, of a high-cost orphan disease in a marginalised minority population in a developing country.

The fair distribution of health resources is critical to health justice. But distributing healthcare equitably requires careful attention to the existing distribution of other resources, and the economic system which produces these inequalities. Health is strongly determined by socioeconomic factors, such as the effects of racism on the health of communities of colour, as well as the broader market-oriented healthcare and pharmaceutical systems that put the pursuit of profit above the alleviation of suffering. Two papers in this issue confront health (...) injustices at different scales, and make far-reaching recommendations for more just healthcare allocation policies. Orphan drugs are those that pharmaceutical companies are unwilling to develop unless they are offered financial incentives to do so. When a target patient group is very small, or very poor, producing drugs is unprofitable. If patients are to benefit from these drugs in a marketised pharmaceutical regime, governments must step in to provide incentives for research and development. Yet government spending ought to prioritise value for money, and is generally guided by a utilitarian framework. In the case of neglected tropical diseases, there is no moral conflict: large numbers of people would benefit greatly from these treatments. However, there are practical limitations: the governments of affected populations are often unable to fund incentives for research and development, and solidarity from elsewhere is limited.1 2 In the case of rare diseases, Global North governments usually can afford to incentivise the development of treatments to serve their populations, but given the small numbers of beneficiaries, doing so seems a questionable use of resources. Many Global North governments make an exception to the general utilitarian heuristic to accommodate the moral intuition that the claims of a person with a rare …. (shrink)

When health budgets are insufficient to provide care for all, allocating resources to treat a person with a rare and expensive disorder entails that we cannot treat at least one person with a more common, less expensive disorder. Since any allocation scheme will entail such trade‐offs, how should prudent policy‐makers, concerned about justice and fairness, allocate their community's health resources? In their article in this issue of the Hastings Center Report, Emily Largent and Steven Pearson frame this problem as a (...) conflict between the “rule of rescue” and utilitarian allocation schemes that try to maximize the benefits produced by a given budget. In his article, Norman Daniels discusses the related problem of the “identified victim bias.” I doubt that the problem of crafting an equitable health policy regarding orphan diseases maps onto either of these factors in a way that sheds light on the key moral issues. (shrink)

In June 2021, an 1856 British Guiana 1c magenta stamp sold for US$8.3m. It is the only known specimen of its kind in existence and on a gram-for-gram basis the most valuable item in the world. Clearly, in some spheres of human engagement, rarity carries a premium. Should this logic be applied in healthcare? Magalhaes thinks not.1 They explore the topic of whether pricing and reimbursement systems should give a premium to orphan drugs for rare diseases. They argue (...) that rarity is irrelevant to pharmaceutical policy on ethical grounds, and instead drug incentives should be prioritised by disease severity. At a time when incentives for orphan medicines are being revisited globally, Magalhaes is provoking an important discussion. The author seeks to disentangle the interwoven concepts of rarity, severity and unmet need that factor into decisions on orphan drug policy. They perhaps overstate the emphasis on rarity within existing regulatory and P&R frameworks. Yes, this is one of the criteria for orphan drug designation, but in payer systems rarity is seldom explicitly referenced. For example, of the five largest European countries, only the United Kingdom formally adjusts willingness-to-pay thresholds by prevalence. In contrast, concepts of severity and unmet need feature widely in global regulatory processes (eg, Breakthrough Therapy designation from …. (shrink)

Un conte de Noël réalisé par Arnaud Desplechin en 2007, raconte un Noël familial dans une petite ville de province du nord de la France (Roubaix). Chacun revient dans la maison de son enfance à cette occasion alors que la mère est atteinte d’une maladie orpheline qui la condamne à court terme et que le frère aîné, Henri est haï par sa sœur et banni de la famille depuis cinq années. L’article analyse ce film où les rapports de genre, s’ils (...) sont constitutifs des relations, n’en restent pas moins soumis au dispositif plus large de la névrose familiale. Il tente de montrer comment le cinéma traduit la complexité des affects et les contradictions tendres et brutales des rapports familiaux. (shrink)

How to handle orphan drugs for rare diseases is a pressing problem in current health-care. Due to the group size of patients affecting the cost of treatment, they risk being disadvantaged in relation to existing cost-effectiveness thresholds. In an article by Niklas Juth it has been argued that it is irrelevant to take indirectly operative factors like group size into account since such a compensation would risk discounting the use of cost, a relevant factor, altogether. In this article (...) we analyze Juth’s argument and observe that we already do compensate for indirectly operative factors, both outside and within cost-effectiveness evaluations, for formal equality reasons. Based on this we argue that we have reason to set cost-effectiveness thresholds to integrate equity concerns also including formal equality considerations. We find no reason not to compensate for group size to the extent we already compensate for other factors. Moreover, groups size implying a systematic disadvantage also on a global scale, i.e. taking different aspects of the health condition of patients suffering from rare diseases into account, will provide strong reason for why group size is indeed relevant to compensate for. (shrink)

The country of Botswana currently has one of the highest HIV infection rates in the world. Government and international aid agencies have undertaken initiatives to address the rapidly growing epidemic, but few measures address the current crisis of care as a key element in that process. In this article, the author uses case study data to highlight how women in Northern Botswana are affected by the increasing burden of caregiving to children who are orphaned as a result of the HIV/aids (...) epidemic. In particular, she describes how the role of women as caregivers in communities has been transformed as a result of the HIV/aids crisis. She suggests that the intersecting cultural patterns of migration and reproduction are central to understanding the spread of the disease in the current emerging crisis of care. (shrink)

Democratic societies find it difficult to reach consensus concerning principles for healthcare distribution in the face of resource constraints. At the same time the need for legitimacy of allocation decisions has been recognised. Against this background, the National Institute for Health and Clinical Excellence (NICE) aspires to meet the principles of procedural justice, specifically the conditions of accountability for reasonableness as espoused by Daniels and Sabin, that is, publicity, relevance, revisions and appeal, and enforcement. Although NICE has adopted a highly (...) standardised approach and continuously publishes key documents on its website, its technology appraisal programme does not fulfil the publicity condition of accountability for reasonableness. Economic models are not made sufficiently transparent to enable public scrutiny, and decision criteria other than cost-effectiveness remain enigmatic. NICE’s reliance on cost-utility analysis and “plausible” cost-per-quality-adjusted life year (QALY) benchmarks further raises serious issues with regard to the relevance condition of accountability for reasonableness. This is illustrated by counterintuitive cost-per-QALY rankings that are difficult to justify using reflective equilibrium methods, and by the current debate surrounding expensive therapies for rare diseases (“orphan” treatments). In addition, an excessive focus on QALYs may stand in the way of exploiting the best available effectiveness evidence. The NICE mechanism for revision and appeals is also more restrictive than provided in accountability for reasonableness. As to the enforcement condition, no effective quality assurance processes are in place for technology assessments, and implementation of guidance remains imperfect. NICE, despite impressive efforts, appears to have a long way to go before meeting the conditions of accountability for reasonableness. (shrink)

Directed cell migration is a fundamental component of numerous biological systems and is critical to the pathology of many diseases. Although the importance of secreted chemoattractant factors in providing navigational cues to migrating cells bearing specific chemoattractant receptors is now well‐established, how the function of these factors is regulated is not so well understood and may be of key importance to the design of new therapeutics for numerous human diseases. While regulation of migration clearly takes place on a (...) number of different levels, it is becoming clear that so‐called ‘atypical’ receptors play a role in scavenging, or altering the localisation of, chemoattractant molecules such as chemokines and complement components. These receptors do this through binding and/or internalising their chemoattractant ligands without activating signal transduction cascades leading to cell migration. The atypical chemokine receptor family currently comprises the receptors D6, DARC and CCX‐CKR. In this review, we discuss the evidence from in vitro and in vivo studies that these receptors play a role in regulating cell migration, and speculate that other orphan receptors may also belong to this family. Furthermore, with the advent of gene therapy on the horizon, the therapeutic potential of these receptors in human disease is also considered. BioEssays 29: 237–247, 2007. © 2007 Wiley Periodicals, Inc. (shrink)

One of the most pressing issues that confronts the Food and Drug Administration (FDA) is learning how to better address and assist in medical product development. FDA needs to prepare today so the agency can efficiently evaluate the technologies of tomorrow. Clearly, this is an area that impacts not only health care consumers but also our economies and financial markets. If the FDA can be a more aggressive part of the solution, they can help not only ease some of the (...) pressures that are driving up health care costs but also help all of us to maximize the value of medical innovations. The high cost of research and development is forcing many companies to make the short-term business decision to focus product development on those molecules that have a much higher potential to recoup expenditures. Unfortunately, this trumps attempts to develop potentially risky but breakthrough products for diseases affecting smaller populations, the orphan drugs. FDA's critical path initiative will enable innovative growth companies to better and more efficiently attack the steep hurdles facing them, allowing them to compete more effectively against the bigger, better-funded players in the market on a more level playing field. That means a real change in the risk/benefit equation for both the emerging growth companies and the public health. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Global Health Careers:Serving the Navajo CommunityMaricruz Merino, Jonathan Iralu, and Sonya ShinGallup Indian Medical Center (GIMC) sits on a hilltop in Gallup, New Mexico, a town of 20,000 in the four corners region of the Southwestern United States. From its third story windows one can see the red cliffs of the nearby Navajo Nation, a 27,000 square mile reservation that reaches into Arizona, northern New Mexico, and the southern (...) edges of Utah. It is a vast, rural landscape that houses more than 350,000 Navajos. For many on the reservation, healthcare is provided by Indian Health Service hospitals such as GIMC."Are you going to stay?" is a common question for new doctors at GIMC. The Navajo know that their geographic location, while beautiful and attractive to many young providers, will also be the reason they leave. It is hard for doctors to be away from their own homelands. Aging parents get sick, [End Page 86] educational opportunities arise, and children who need to be near extended family are born. But to the Navajo, the story of an individual provider is not so important or memorable. All they know is that providers come and go."Are you here to experiment on us?" is yet another question. Years of exploitation and efforts to destroy traditional ways and language have made many Navajo wary of healthcare providers, no matter how genuine their intentions. Many are so fearful of the hospital—they regard it as "the place to go die."Yet despite this initial suspicion, the Navajo are welcoming people at heart, and tend to develop relationships of trust with their providers. Parents will begin to talk about their grief over a son that has committed suicide or a daughter who died from alcoholic cirrhosis. The elderly will tell you how they care for their five orphaned grandchildren while they can barely take care of their own diabetes. A carpenter tells you he has not worked in a year and feels worthless. An HIV-positive woman will tell you she has been sleeping in a dry river bed because she has no place to go. It quickly becomes apparent that as a physician you will be treating patients with enormous social challenges in addition to complex medical conditions.The origins of the Federal Government's involvement in the healthcare of American Indians and Alaskan Natives (AI/ANs) in the 19th century arose out of both legal obligation and concern for self- preservation. Health services were promised to AI/ ANs in exchange for land, settlements, and agreements. In addition, infectious diseases endemic on reservations as a consequence of crowding and abject poverty, including smallpox and tuberculosis, were seen as a major public health concern. The responsibility of Native American health was first granted to the War Department, then to the Bureau of Indian Affairs, and finally to the Public Health Service in 1955 under the heading of the IHS, or Indian Health Service (U.S. Commission on Civil Rights, 2004; National Library of Medicine, 1994).Since then, the IHS has had many successes. Vaccination rates have gone up, and rates of pneumonia and tuberculosis have gone down significantly. Maternal and infant mortality have declined, and life expectancy has increased (Indian Health Services, 1999). Nonetheless, these improvements remain overshadowed by glaring health disparities among AI/ANs across a broad spectrum of diseases, both communicable and non-communicable, acute and chronic. Native Americans experience higher rates of obesity, diabetes, and cardiovascular disease than the general United States population. They are also more likely to die from alcohol-related causes and in accidents. Life expectancy remains more than five years less than that of the general U.S. population (U.S. Commission on Civil Rights, 2004; U.S. Department of Health and Human Services, 2000).Underlying these health indicators is the continued impoverished status of most AI/ANs. In Navajo, almost half of the population lives below the poverty line. According to the Navajo Nation, the current unemployment rate is 42% (Navajo Nation Department of Economic Development, 2011). Many Navajo on the reservation do not have running water or electricity. They heat with wood, which they chop and haul themselves—regardless... (shrink)

To date, ethics discussions about stem cell research overwhelmingly have centered on the morality and acceptability of using human embryonic stem cells. Governments in many jurisdictions have now answered these “first-level questions” and many have now begun to address ethical issues related to the donation of cells, gametes, or embryos for research. In this commentary, we move beyond these ethical concerns to discuss new themes that scientists on the forefront of NRM development anticipate, providing a preliminary framework for further discussion (...) between scientists and ethicists. Fostering strong partnerships between neuroscientists and ethicists that operate and collaborate within this evolving framework will maximize the translation of NRM discoveries on the brain into cures that are safe and address the needs of science and society. (shrink)

Use of humanities content in American medical education has been debated for well over 60 years. While many respected scholars and medical educators have purported the value of humanities content in medical training, its inclusion remains unstandardized, and the undergraduate medical curriculum continues to be focused on scientific and technical content. Cited barriers to the integration of humanities include time and space in an already overburdened curriculum, and a lack of consensus on the exact content, pedagogy and instruction. Edmund Pellegrino, (...) physician and scholar of the latter twentieth century, spent much of his professional life promoting the value and importance of the humanities in medical education, seeking the best way to incorporate and teach this content in clinically relevant ways. His efforts included the founding of multiple enterprises starting in the 1960s and 1970s to promote human values in medical education, including the Society for Health and Human Values and its Institute on Human Values in Medicine. Regardless of his efforts and those of many others into the current century, the medical humanities remains a curricular orphan, unable to find a lasting home in medical education and training. (shrink)

Prabhpal Singh has defended a relational account of the difference in moral status between fetuses and newborns. Newborns stand in the parent-child relation while fetuses do not, and standing in the parent-child relationship brings with it higher moral status for newborns. Orphans pose a problem for this account because they do not stand in a parent-child relationship. I argue that Singh has not satisfactorily responded to the problem.

Although popular, I argue that the International Committee of Medical Journal Editors (ICMJE) account of authorship is flawed. It inadvertently allows for practices that it was designed to prevent. In addition, it creates a new category of authorless papers—orphan papers. The original World Association of Medical Editors (WAME) criterion is preferable.

This article examines the attempt by the Kingdom of Morocco—a country of pivotal geopolitical importance in the late 1970s and early 1980s—to secure a research reactor. It finds that by treating that reactor as a diplomatic object, we can observe the different diplomatic frameworks in which that object was conceived of, contextualized, and negotiated. The historical emergence of these frameworks occurred in close relationship with the IAEA, which acted as an intermediary linking various administrations, programs, and countries, including Morocco. In (...) the end, this history reveals that the late Cold War nuclear world involved multilateral actions and forces, some of which encouraged Morocco in its bid to acquire a reactor, but others of which left that same reactor orphaned and unfinished. (shrink)

In this paper, I urge feminists to re-center fetal moral status in their theorizing about abortion. I argue that fundamental feminist normative commitments are at odds with efforts to de-emphasize fetal moral status: The feminist commitment to ensuring care for dependents supports surprising conclusions with regard to the ethics of abortion, and the feminist commitment to politicizing the personal has surprising conclusions regarding the politics of abortion. But these feminist insights also support the conclusion that, conditional on fetal moral status, (...) care for unwanted fetuses would be a social obligation that only derivatively falls to women who are unwillingly pregnant. (shrink)

I offer a response to an objection to my account of the moral difference between fetuses and newborns, an account that seeks to address an analogy between abortion and infanticide which is based on the apparent equality of moral value of fetuses and newborns.

A number of advances in assisted reproduction have been greeted by the accusation that they would produce children ‘without parents’. In this paper I will argue that while to date these accusations have been false, there is a limited but important sense in which they would be true of children born of a reproductive technology that is now on the horizon. If our genetic parents are those individuals from whom we have inherited 50% of our genes, then, unlike in any (...) other reproductive scenario, children who were conceived from gametes derived from stem cell lines derived from discarded IVF embryos would have no genetic parents! This paper defends this claim and investigates its ethical implications. I argue that there are reasons to think that the creation of such embryos might be morally superior to the existing alternatives in an important set of circumstances. (shrink)

Christians care for orphans and children without parental care in different forms. However, in the Global South, care is primarily provided in orphanages or large residential settings. Despite good intentions, there are limitations to provide a nurturing family environment for the children in such care environment. With current knowledge of alternative child care and in light of the holistic ministry, this article suggests an approach for the church to care for orphans and children at risk by focusing on the family (...) and the local community. Additionally, simple steps to transition to holistic orphan care are offered. (shrink)

In infancy, all primates require a caregiver who meets their physical needs, such as food and protection (among many others), and their affective, cognitive, and social needs (in some species, this requirement extends until the primate is a juvenile). The caregiver is essential for primate infant survival and social and cognitive development. For that reason, infants are greatly affected if they lose their caregivers; the effects of becoming an orphan range from being unable to survive to behavioral and physiological (...) consequences that last through adulthood. This entry provides an overview of relevant aspects of the study of primate orphans such as survival rates, adoption, variables in the adoption process, the effects of losing a mother, and orphans in sanctuaries. (shrink)

At least seven orphan members of the nuclear receptor superfamily are transcriptionally regulated by the steroid hormone ecdysone and expressed during the onset of Drosophila metamorphosis. A recent paper provides functions for two of these receptors, E75B and DHR3, through trans‐regulation and heterodimerization(1). DHR3 appears to function as a switch that defines the transition from a late larva to a prepupa, and E75B functions as a timer that modulates this transition. This study provides a biological function for orphan (...) receptor interactions during development. (shrink)

This study investigates the literary references to orphans in writings amongst the Qumran texts that were written in Hebrew and can be associated with the sectarian Qumran movement. The study focuses on passages where forms of the word -•-• are used. These include the Damascus Document, Hodayot and Barkhi Nafshiª. The investigation concludes that the references to orphans in these passages do not have the same rhetorical functions. In CD 6, the wordings of authoritative scriptures are adapted to portray orphans (...) and widows as the victims of wrongdoing. In 1QHª and 4Q434, however, orphans are mentioned in hymns that praise the Lord's positive treatment of needy people. (shrink)

Children and pregnant women are often excluded from clinical research. This has resulted in a paucity of evidence on how medicines work for fetuses, neonates, infants, and adolescents. It also raises bioethics, scientific, and public health concerns. For over half a century, doctors have prescribed medicines to children largely on the basis of how they work in adults, despite children’s varied physiologies and differences in how their bodies absorb and metabolize drugs. Regulations and legislation have led to an increase in (...) the number of pediatric studies and to better drug labeling. However, children at all stages of their lives often remain “therapeutic orphans” owing to insufficient evidence about how medicines work for them. (shrink)

This paper examines what it is for a condition to be a disease. It falls into two sections. In the first I examine the best existing account of disease (as proposed by Christopher Boorse) and argue that it must be rejected. In the second I outline a more acceptable account of disease. According to this account, by disease we mean a condition that it is a bad thing to have, that is such that we consider the afflicted person to have (...) been unlucky, and that can potentially be medically treated. All three criteria must be fulfilled for a condition to be a disease. The criterion that for a condition to be a disease it must be a bad thing is required to distinguish the biologically different from the diseased. The claim that the sufferer must be unlucky is needed to distinguish diseases from conditions that are unpleasant but normal, for example teething. Finally, the claim that for a condition to be a disease it must be potentially medically treatable is needed to distinguish diseases from other types of misfortune, for example economic problems and legal problems. (shrink)

Conceptual analysis of health and disease is portrayed as consisting in the confrontation of a set of criteria—a “definition”—with a set of cases, called instances of either “health” or “ disease.” Apart from logical counter-arguments, there is no other way to refute an opponent’s definition than by providing counter-cases. As resorting to intensional stipulation is not forbidden, several contenders can therefore be deemed to have succeeded. This implies that conceptual analysis alone is not likely to decide between naturalism and normativism. (...) An alternative to this approach would be to examine whether the concept of disease can be naturalized. (shrink)

Rare genetic diseases collectively impact millions of individuals in the United States. These patients and their families share many challenges including delayed diagnosis, lack of knowledgeable providers, and limited economic incentives to develop new therapies for small patient groups. As such, rare disease patients and families often must rely on advocacy, including both self-advocacy to access clinical care and public advocacy to advance research. However, these demands raise serious concerns for equity, as both care and research for a given (...) disease can depend on the education, financial resources, and social capital available to the patients in a given community. In this article, we utilize three case examples to illustrate ethical challenges at the intersection of rare diseases, advocacy and justice, including how reliance on advocacy in rare disease may drive unintended consequences for equity. We conclude with a discussion of opportunities for diverse stakeholders to begin to address these challenges. (shrink)