Is knowledge in various domains needed to understand bioethical issues?

Abstract

Researchers agree that an interdisciplinary approach should be taken to address bioethical issues at school. Little is known about the knowledge students need to be able to understand and take part in discussions about these issues. We investigate the relationship between 79 students’ prior knowledge in various domains and their ability to recall and produce arguments about a bioethical issue. Our results partially confirm theoretical assumptions presented in, and findings from, related studies. Knowledge in various domains facilitates understanding of bioethical issues and facilitates recall and development of related arguments. Addressing bioethical issues at school has numerous benefits for students, for example, it allows them to develop and employ knowledge in various domains and to see how it interconnects.     

‘Bioethical Realism’: A Framework for Implementing Universal Research Ethics

Implementation of existing ethical guidelines for international collaborative medical and health research is still largely controversial in sub‐Saharan Africa for two major reasons: One, they are seen as foreign and allegedly inconsistent with what has been described as an ‘African worldview’, hence, demand for their strict implementations reeks of ‘bioethical imperialism’. Two, they have other discernible inadequacies – lack of sufficient detail, apparent as well as real ambiguities, vagueness and contradictions. Similar charges exist(ed) in other non‐Western societies. Consequently, these guidelines have been correctly judged as an inadequate response to the complex and ever shifting dilemmas met by researchers and research regulators in the field. This paper proposes a framework for effective implementation of existing guidelines without much worry about bioethical imperialism and other inadequacies. This framework is proposed using an analogy of Legal Realism, specifically its key assertions on how, in reality, judicial systems operate using general legal rules to settle specific cases. Legal realists assert that in judicial decision‐making, general legal rules do not totally dictate court decisions in specific cases. This analogy is used to coin a new term, ‘Bioethical Realism.’ The framework suggests that local Research Ethics Committees ought to be construed as analogues of judicial courts with the resulting implications. Consequently, just like legal rules are general rules that do not always dictate court decisions, similarly international bioethical guidelines are general ethical rules that should not always dictate local RECs’ decisions and such decisions (ought to) enjoy considerable immunity from outsiders.     

Public involvement in pharmacogenomics research: a national survey on public attitudes towards pharmacogenomics research and the willingness to donate DNA samples to a DNA bank in Japan

To assess the attitudes of the Japanese general public towards pharmacogenomics research and a DNA bank for identifying genomic markers associated with ADRs and their willingness to donate DNA samples, we conducted a national survey for 1,103 Japanese adults from the general public, not a patient population. The response rate was 36.8%. The majority of the respondents showed a positive attitude towards pharmacogenomics research (81.0%) and a DNA bank (70.4%). Considering fictitious clinical situations such as taking medications and experiencing ADRs, the willingness to donate DNA samples when experiencing ADRs (61.7%) was higher than when taking medications (45.3%). Older generations were significantly associated with a decreased willingness to donate (OR = 0.45, CI 0.28–0.72 in 50s. OR = 0.49, CI: 0.31–0.77 in 60s). Positive attitudes towards pharmacogenomics research, a DNA bank, blood/bone marrow/organ donation were significantly associated with an increased willingness. However, the respondents had the following concerns regarding a DNA bank: the confidentiality of their personal information, the manner by which research results were utilized and simply the use of their own DNA for research. In order to attain public understanding to overcome these concerns, a process of public awareness should be put into place to emphasize the beneficial aspects of identifying genomic markers associated with ADRs and to address these concerns raised in our study. Further study is needed to assess the willingness of actual patients taking medications in real situations, since the respondents in our study were from the general public, not a patient population, and their willingness was assessed on the condition of assuming that they were patients taking medications.     

A Pharmacovigilance Approach for Post-Marketing in Japan Using the Japanese Adverse Drug Event Report (JADER) Database and Association Analysis

BackgroundRapid dissemination of information regarding adverse drug reactions is a key aspect for improving pharmacovigilance. There is a possibility that unknown adverse drug reactions will become apparent through post-marketing administration. Currently, although there have been studies evaluating the relationships between a drug and adverse drug reactions using the JADER database which collects reported spontaneous adverse drug reactions, an efficient approach to assess the association between adverse drug reactions of drugs with the same indications as well as the influence of demographics (e.g. gender) has not been proposed.ConclusionsDifferent combinations of adverse drug reactions were noted between the antidepressants. In addition, the reported adverse drug reactions differed by gender. This approach using a large database for examining the associations can improve safety monitoring during the post-marketing phase.     

Probes for Double Helical DNA Sequence Information: Molecular Mechanics Study of a Proposed Model

Abstract

The biological activity of many molecules which bind to double helical DNA is related to the sequence specificity of their binding. The development of new substances of this type is challenging; a general solution to the problem does not exist. A new mechanism for small molecule-duplex DNA interaction termed intercalative displacement is proposed. The approach is promising for the design of new substances which will recognize sequence information on DNA Molecular mechanics calculations in the absence of solvent and counterions predict that the proposed model is structurally and energetically closely related to the well known process of standard intercalation. The implications of these calculations for experimental studies are discussed.     

Mainstreaming Sex and Gender Analysis in Public Health Genomics

BackgroundThe integration of genome-based knowledge into public health or public health genomics (PHG) aims to contribute to disease prevention, health promotion, and risk reduction associated with genetic disease susceptibility. Men and women differ, for instance, in susceptibilities for heart disease, obesity, or depression due to biologic (sex) and sociocultural (gender) factors and their interaction. Genome-based knowledge is rapidly increasing, but sex and gender issues are often not explored.ObjectiveTo explore the implications of a sex and gender analysis for PHG.MethodsWe explore genome-based knowledge in relation to sex and gender aspects using depression as an example, gender equality, and the intersection of sex and gender with other social stratifiers such as ethnic background or socioeconomic status.ResultsWe advocate a sex- and gender-sensitive genomics research agenda alongside studies that provide sex-disaggregated data rather than controls based on sex. Such a research agenda is needed to guide research on how genomics is understood and perceived by men and women across groups, and for the equitable and responsible translation of such knowledge into the public health domain.ConclusionsIncluding sex and gender analysis in PHG research will not only shed more light on phenomena such as diseases with a higher prevalence in either men or women, but will ultimately lead to gendered innovations by way of exploring how gendered and cultural environments increase or safeguard genetic predispositions.     

HIV+/AIDS related bioethical issues in Japan

Annual and cumulative incidences of HIV+ and AIDS in patients reported by the AIDS Surveillance Committee of the Ministry of Health and Welfare are cited to illustrate some characteristics in Japan: nearly 59% of either HIV+ or AIDS patients were infected through injection of blood products or by blood transfusion. A number of plaintiffs have sued the Japanese government and pharmaceutical companies since 1989, but no judicial decisions have yet been made. The incidence of HIV decreases for each of the following routes of infection: the second highest route of transmission being heterosexual, followed by bisexual and unconfirmed or unknown cases, and less frequently homosexual, drug use and lastly via vertical transmission. The most serious bioethical problems with HIV+ and AIDS patients in Japan is the social segregation of these patients. There are many emotional fears among the general public and medical personnel about AIDS because of their inadequate scientific knowledge of this disease. The Japan Hospital Association is doing The Stop AIDS Campaign and made several surveys. Japan has become increasingly aware of the importance of AIDS education and a great deal of effort is being made to enhance bioethical consideration.     

Peer Support Workers in Health: A Qualitative Metasynthesis of Their Experiences

ObjectivePeer support models, where an individual has a specific illness or lifestyle experience and supports others experiencing similar challenges, have frequently been used in different fields of healthcare to successfully engage hard-to-reach groups. Despite recognition of their value, the impact of these roles on the peer has not been systematically assessed. By synthesising the qualitative literature we sought to review such an impact, providing a foundation for designing future clinical peer models.MethodsSystematic review and qualitative metasynthesis of studies found in Medline, CINAHL or Scopus documenting peer worker experiences.Results1,528 papers were found, with 34 meeting the criteria of this study. Findings were synthesised to reveal core constructs of reframing identity through reciprocal relations and the therapeutic use of self, enhancing responsibility.ConclusionsThe ability of the Peer Support Worker to actively engage with other marginalised or excluded individuals based on their unique insight into their own experience supports a therapeutic model of care based on appropriately sharing their story. Our findings have key implications for maximising the effectiveness of Peer Support Workers and in contributing their perspective to the development of a therapeutic model of care.     

Pharmacogenetics and pharmacogenomics in oncology therapeutic antibody development

Pharmacogenetics and pharmacogenomics are keys to the success of personalized medicine, prescribing drugs based on a patient's individual genetic and biological profile. In this review, we will focus on the application of pharmacogenetics and pharmacogenomics in developing monoclonal antibody (MAb) therapeutics in oncology. The significance of pharmacogenomics in MAb therapeutics is highlighted by the association between polymorphisms in Fc receptors and clinical response to anti-CD20 MAb rituximab (Rituxan) or anti-ganglioside GD2 MAb 3F8, as well as the potential link between polymorphisms in HER2 and cardiac toxicity in patients treated with the anti-HER2 MAb trastuzumab (Herceptin). The dependence on gene copy number or expression levels of HER2 and epidermal growth factor receptor (EGFR) for therapeutic efficacy of trastuzumab and cetuximab (Erbitux), respectively, supports the importance of selecting suitable patient populations based on their pharmacogenetic profile. In addition, a better understanding of target mutation status and biological consequences will benefit MAAb development and may guide clinical development and use of these innovative therapeutics. The application of pharmacogenetics and pharmacogenomics in developing MAb therapeutics will be largely dependent on the discovery of novel surrogate biomarkers and identification of disease- and therapeutics-relevant polymorphisms. Challenges and opportunities in biomarker discovery and validation, and in implementing clinical pharmacogenetics and pharmacogenomics in oncology MAb development and clinical practice will also be discussed.     

Retrospective analysis of census data on general practitioners who qualified in South Asia: who will replace them as they retire?

ObjectivesTo determine the number and geographical distribution of general practitioners in the NHS who qualified medically in South Asia and to project their numbers as they retire.DesignRetrospective analysis of yearly data and projection of future trends.SettingEngland and Wales.SubjectsGeneral practitioners who qualified medically in the countries of Bangladesh, India, Pakistan, and Sri Lanka and who were practising in the NHS on 1 October 1992.Results4192 of 25 333 (16.5%) of all unrestricted general practitioners practising full time on 1 October 1992 qualified in South Asian medical schools. The proportion varied by health authority from 0.007% to 56.5%. Roughly two thirds who were practising in 1992 will have retired by 2007; in some health authorities this will represent a loss of one in four general practitioners. The practices that these doctors will leave seem to be in relatively deprived areas as measured by deprivation payments and a health authority measure of population need.ConclusionMany general practitioners who qualified in South Asian medical schools will retire within the next decade. The impact will vary greatly by health authority. Those health authorities with the greatest number of such doctors are in some of the most deprived areas in the United Kingdom and have experienced the most difficulty in filling vacancies. Various responses will be required by workforce planners to mitigate the impact of these retirements.

Key messages

• Currently, one in six general practitioners practising full time in the NHS qualified medically in a South Asian medical school; two thirds are likely to retire by 2007
• It is unlikely that doctors who qualify in South Asia will be a source of general practice recruitment in the future
• The posts from which South Asian qualifiers are retiring may be more difficult to fill because they are often in practices in areas of higher need
• There is extreme variation in the proportion of total general practitioners who are South Asian qualifiers; flexibility for policy responses should be maintained

     

Pharmacogenomics: Catechol O-Methyltransferase to Thiopurine S-Methyltransferase

1. Pharmacogenomics is the study of the role of inheritance in variation in the drug response phenotype—a phenotype that can vary from adverse drug reactions at one end of the spectrum to lack of therapeutic efficacy at the other.2. The thiopurine S-methyltransferase (TPMT) genetic polymorphism represents one of the best characterized and most clinically relevant examples of pharmacogenomics. This polymorphism has also served as a valuable “model system” for studies of the ways in which variation in DNA sequence might influence function.3. The discovery and characterization of the TPMT polymorphism grew directly out of pharmacogenomic studies of catechol O-methyltransferase (COMT), an enzyme discovered by Julius (Julie) Axelrod and his coworkers.4. This review will outline the process by which common, functionally significant genetic polymorphisms for both COMT and TPMT were discovered and will use these two methyltransferase enzymes to illustrate general principles of pharmacogenomic research—both basic mechanistic and clinical translational research—principles that have been applied to a series of genes encoding methyltransferase enzymes.     

Genetic polymorphism of pharmacogenomic VIP variants in the Deng people from the Himalayas in Southeast Tibet

Abstract

Little is known about polymorphic distribution of pharmacogenes among ethnicities, including the Deng people. In this study, we recruited 100 unrelated, healthy Deng people and genotyped them with respect to 76 different single-nucleotide polymorphisms by the PharmGKB database. Our results first indicated that the polymorphic distribution of pharmacogenes of the Deng people is most similar to CHD, suggesting that Deng people have a closest genetic relationship with CHD. Our data will enrich the database of pharmacogenomics and provide a theoretical basis for safer drug administration and individualized treatment plans, promoting the development of personalized medicine.     

Tailor-made pharmacotherapy: future developments and ethical challenges in the field of pharmacogenomics

Pharmacogenomics is the study of the myriad interactions between genes and pharmacotherapy. Developments in pharmacogenomics have changed and will affect pharmaceutical research, drug development and the practice of medicine in a significant way. In this article, we make an inventory of the ethical implications that might arise as a result of possible developments in pharmacogenomics and investigate whether the present ethical framework will be able to adequately answer arising questions. We think that many of the questions related to the consequences of pharmacogenomics are answerable along the lines of present ethical thinking. We also believe, however, that many 'changes of degree' may result in a 'change of kind.' We therefore think that pharmacogenomics may potentially have such a profound influence on scientific research and the pharmaceutical industry, the practice of medicine and society at large, that this will generate its own unique dynamic, which will require new ethical research. We suggest that the notion of 'responsibility' will be a major focus of such research.     

Public Support for Conserving Bird Species Runs Counter to Climate Change Impacts on Their Distributions

There is increasing evidence that global climate change will alter the spatiotemporal occurrences and abundances of many species at continental scales. This will have implications for efficient conservation of biodiversity. We investigate if the general public in Denmark are willing to pay for the preservation of birds potentially immigrating and establishing breeding populations due to climate change to the same extent that they are for native species populations currently breeding in Denmark, but potentially emigrating due to climate change. We find that Danish citizens are willing to pay much more for the conservation of birds currently native to Denmark, than for bird species moving into the country – even when they are informed about the potential range shifts associated with climate change. The only exception is when immigrating species populations are under pressure at European level. Furthermore, people believing climate change to be man-made and people more knowledgeable about birds tended to have higher WTP for conservation of native species, relative to other people, whereas their preferences for conserving immigrant species generally resembled those of other people. Conservation investments rely heavily on public funding and hence on public support. Our results suggest that cross-country coordination of conservation efforts under climate change will be challenging in terms of achieving an appropriate balance between cost-effectiveness in adaptation and the concerns of a general public who seem mostly worried about protecting currently-native species.     

2009 Society for Medical Anthropology Conference: From Race to Repositories: Bioethics in a Genomics Age

Medical anthropologist Barbara Koenig spoke on the intersection of bioethics and genomics at the 2009 Society for Medical Anthropology Conference at Yale University in New Haven, Connecticut.Medical anthropologist Barbara Koenig is at the forefront of numerous endeavors that seek to understand race in the age of genomics and protect human subjects with regard to DNA repositories. Through a dialogue ranging from the history and critiques of bioethics to her own research projects, Koenig brought her respect and excitement for the anthropology found in biomedicine to the 2009 Society for Medical Anthropology conference at Yale University in September.As a whole, the space in which bioethics operates does not constitute a “field” in the traditional sense. It is an amalgam of approaches to the social, ethical, and cultural issues surrounding biology and medicine. While the prevalent medical ethic for 2,500 years has been understood to be embodied in the Hippocratic Oath [1], the modern age of biomedical research and clinical practice demands more careful inspection of ethical issues in biology and medicine. This precise space is where bioethics has found fertile ground for investigation. For Koenig, anthropological analysis and, more specifically, empirical ethnographic study are critical tools to tease apart the complexities of bioethical issues.Recently, Koenig, a professor of medicine at the Mayo Clinic, has considered the definitions of race in light of the emerging work of genomics [2,3]. Her book, Revisiting Race in a Genomic Age, argues that the complex definitions of race are an interesting blend of biological differences and cultural traditions. Often in modern society, the unity assumed among a racial group is at odds with the underlying biological diversity revealed by genomics. And yet individuals in our species are much more related to one another than, for example, any two chimps are related. It is clear from the much-cited work of the Human Genome Project [4,5] and the International HapMap Consortium [6] that genomics will have a deeply profound impact on how we understand our ancestry and how easily individuals will be able to trace their own origins using modern genetic technologies.Hints at new implications in personalized medicine also have come to light, showing that different patient populations, distinguished by race, can have significantly different responses to drugs [7,8]. Increasingly, race is used as a categorization to parse individuals for the purposes of biomedical research. These categories are themselves areas of contention, as they are socially constructed. Individuals may identify themselves with different racial categories depending on the context in which the identifiers are provided. Furthermore, it is unclear what implications can be drawn from the studies in which researchers are asked to conclude something about a social identity based on biological data. Research in these areas undoubtedly will provide insightful anthropological analysis in the coming years.Much of bioethics is concerned with the issues surrounding new medical technologies and their impact on society. In this same vein, the advent of sequencing databases and direct-to-consumer genetic tests has had broad implications for the participants. At the Mayo Clinic, Koenig is working on the development of a centralized biobank. This facility will store DNA samples collected from patients with a wide range of diseases and enable easy access for clinicians and scientists interested in studying a given disease. However, as with any collection of information, there is a question of access. Who can see what information? How will this be regulated? And to what extent is informed consent required for each of the future uses of the collected sample?There has been much public debate regarding the ethical use of forensic DNA databases [9,10] and yet less public consideration concerning the medical DNA databases. Koenig spoke of attempts to create community understanding beyond the informed consent standard. An auxiliary issue related to the social impacts of new genetic methods is the emergence of direct-to-consumer genetic testing. Currently, certain companies market to the public with the promise of assessing the customer’s genetic profile in order to identify genetic risk factors for disease. Without the intermediary of a health care provider to validate the analysis and contextualize the risk, these tests can have an alarming and bewildering effect on consumers. How should one understand an 8 percent increase in colorectal cancer risk relative to the general population? Certainly, these new technologies and the companies pushing them directly to the consumer public are of profound anthropological interest.While some anthropologists analyze trends and conduct surveys to understand their subjects, Koenig has entrenched herself within the clinic and on advisory boards to shape the outcome of bioethical issues facing our society in a time of ever-changing technologies. She has done so with a firm foundation in the historical perspective and practical ethic of biomedicine.     

Public involvement in pharmacogenomics research: a national survey on patients’ attitudes towards pharmacogenomics research and the willingness to donate DNA samples to a DNA bank in Japan

To assess the attitude of Japanese patients towards pharmacogenomics research and a DNA bank for identifying genomic markers associated with adverse drug reactions (ADRs) and their willingness to donate DNA samples, we conducted a survey of 550 male and female patients. The majority of the respondents showed a positive attitude towards pharmacogenomics research (87.6%) and a DNA bank (75.1%). The willingness to donate DNA samples when experiencing severe ADRs (55.8%) was higher than when taking medications (40.4%). Positive attitudes towards a DNA bank and organ donation were significantly associated with an increased willingness to donate. Though the level of positive attitude in the patient population was higher than that in the general public in our former study (81.0 and 70.4%, respectively), the level of the willingness of patients to donate was 40.4% when taking medications and 55.8% when experiencing severe ADRs which was lower than that of the general public in our former study (45.3 and 61.7%). The results suggested that the level of true willingness in the patient population was lower than that of the general public considering the fictitious situation presented to the public (to suppose that they were patients receiving medication). It is important to assess the willingness of patients who are true potential donors, not the general public.     

Technoscientific bespoking: Animals,publics and the new genetics

This paper examines the public understanding of science, especially biotechnology and the new genetics, in light of the symbolic roles of animals in the constitution of cultural identities. As such, the paper expands on the critical approach to public understanding of science, with its emphasis upon the way local identities impact upon the apprehension of, and trust in, science and scientific institutions. In particular, the new genetics raises issues about what sorts of broader public identities are mobilized. It is argued that, on the one hand, the complex symbolic role of animals is linked to a wide and contradictory range of modern Western identities, and thus potentially to volatility in the public's response to such biotechnological innovation. On the other, technoscientific bespoking, by rendering animals 'ready-to-order', might catastrophically curtail the symbolic role of animals in human identities, and thus provoke a general anxiety toward new genetics. Some political and research implications of the analysis are briefly explored.     

Improving the health behaviours of elderly people: randomised controlled trial of a general practice education programme

ObjectivesTo establish the effect of an educational intervention for general practitioners on the health behaviours and wellbeing of elderly patients.DesignRandomised controlled trial with 1 year follow up.SettingMetropolitan general practices in Melbourne, Australia.Subjects42 general practitioners and 267 of their patients aged over 65 years.InterventionEducational and clinical practice audit programme for general practitioners on health promotion for elderly people.ResultsPatients in the intervention group had increased (a) walking by an average of 88 minutes per fortnight, (b) frequency of pleasurable activities, and (c) self rated health compared with the control group. No change was seen in drug usage, rate of influenza vaccination, functional status, or psychological wellbeing as a result of the intervention. Extrapolations of the known effect of these changes in behaviour suggest mortality could be reduced by 22% if activity was sustained for 5 years.ConclusionsEducation of the general practitioners had a positive effect on health outcomes of their elderly patients. General practitioners may have considerable public health impact in promotion of health for elderly patients.

Key messages

• Few educational interventions for doctors have shown benefit to the health of patients
• Elderly people were identified in the UK health initiatives as in need of additional attention, and levels of health protective behaviours were low in community surveys
• A multifaceted educational intervention for general practitioners was effective in improving walking behaviour, self rated health status, and the frequency of social contacts in elderly patients
• General practitioners are effective in improving health and health behaviours in their elderly patients

     

A relational theory of biological systems II

The general Theory of Categories is applied to the study of the (M, R)-systems previously defined. A set of axioms is provided which characterize “abstract (M, R)-systems”, defined in terms of the Theory of Categories. It is shown that the replication of the repair components of these systems may be accounted for in a natural way within this framework, thereby obviating the need for anad hoc postulation of a replication mechanism. A time-lag structure is introduced into these abstract (M, R)-systems. In order to apply this structure to a discussion of the “morphology” of these systems, it is necessary to make certain assumptions which relate the morphology to the time lags. By so doing, a system of abstract biology is in effect constructed. In particular, a formulation of a general Principle of Optimal Design is proposed for these systems. It is shown under what conditions the repair mechanism of the system will be localized into a spherical region, suggestive of the nuclear arrangements in cells. The possibility of placing an abstract (M, R)-system into optimal form in more than one way is then investigated, and a necessary and sufficient condition for this occurrence is obtained. Some further implications of the above assumptions are then discussed.