Emergence of norms for biomedical research. At the origin of the Huriet law (1975-1988)

The French law for the Protection of persons involved in biomedical research, known as "Loi Huriet", defines the frame in which biomedical experimentations on human subjects can take place. Insisting on the emergent character of the norms (laws, scientific standards...) for clinical research in France, this paper presents the general context in which such a law was promulgated. It gives an historical focus on its principal dispositions and underlines the conceptual issues raised by the public acknowledgment of the existence of scientific investigations on humans. This paper contributes to the debate on the meaning of the main notions of the French normative system applying to biomedical researches (protection of the person, individual direct benefice...)     

Features of the Bioethical Regulation of Human Studies in Aerospace and Maritime Medicine

The author considers the specific features of applying the universally accepted standards of biomedical ethics to human research in aerospace and maritime medicine. The extreme factors that act on human subjects may be a menace to their health and physical and mental well-being. Therefore, medical information that comes from human studies is important not only scientifically, but also practically as the basis for revealing and preventing the risks related to such factors and for ensuring the safety of both human subjects and members of missions who may be exposed to such impacts in the future. This makes it necessary to not only strictly adhere to the basic standards of biomedical ethics, but also adapt some of them to the priority task of ensuring human safety under extreme conditions. Among other problems, the author discusses possible ways of correcting the scope of application of bioethical principles, such as confidentiality, voluntariness, and the right to refuse from or stop taking part in an experiment.     

The Concept of Risk in Biomedical Research Involving Human Subjects

An established ethical principle of biomedical research involving human subjects stipulates that risk to subjects should be proportionate to an experiment's potential benefits. Sometimes this principle is imprecisely stated as a requirement that 'risks and benefits' be balanced. First, it is noted why this language is imprecise. Second, the persistence of such language is attributed to how it functions as a rhetorical trope. Finally, an argument is made that such a trope is infelicitous because it may not achieve its intended persuasive purposes. More importantly, it should be avoided because it masks the important role that chance plays in clinical research. Risk is the possibility of harm. As a precondition of harm it is unintended and undesirable in projects of biomedical research. It requires ethical vigilance. As a vehicle of chance, however, it is both intended and desirable. It requires methodological appreciation.     

Ethical Principles for Conducting Fieldwork

Federal regulations to protect human subjects assume a particular relationship between experimenter and subject based upon biomedical research. Because this relationship is not found in every type of research, the regulations are not universally applicable. Relationships between those who study and those who are studied vary with the kind of research. Such variations depend on the relative power and control of the researcher, the direction of interaction, and the level of possible harms and benefits. Measured on these continua, fieldwork is at the opposite end of the spectrum from biomedical research. Consequently, the ethical system on which federal regulations are chiefly based—using utilitarian risk-benefit calculations—becomes ineffective and inappropriate when applied to proposed fieldwork. Here, investigators have relatively little power and less control of the setting and context of research, interaction flows in two directions, and calculable harms and benefits are comparatively low. Various models of fieldwork are described, each having differing relationships between investigators and subjects. It is suggested that the Kantian categorical imperative, with its principle of respect for human autonomy, might be useful in judging the ethical adequacy of these varieties of fieldwork. [fieldwork, ethical principles, research relationships, federal regulations, risk-benefit calculations]     

Not Fit for Purpose: The Ethical Guidelines of the Indian Council of Medical Research

In 2006, the Indian Council of Medical Research (ICMR) published its ‘Ethical guidelines for Biomedical Research on human participants’. The intention was to translate international ethical standards into locally and culturally appropriate norms and values to help biomedical researchers in India to conduct ethical research and thereby safeguard the interest of human subjects. Unfortunately, it is apparent that the guideline is not fit for purpose. In addition to problems with the structure and clarity of the guidelines, there are several serious omissions and contradictions in the recommendations. In this paper, we take a close look at the two key chapters and highlight some of the striking flaws in this important document. We conclude that ethics committees and national authorities should not lose sight of international ethical standards while incorporating local reality and cultural and social values, as focusing too much on the local context could compromise the safety of human subjects in biomedical research, particularly in India.     

Comparison of the frequencies of major histocompatibility (MHC) class-II DQA1 and DQB1 alleles in Indian and Chinese rhesus macaques (Macaca mulatta)

The major histocompatibility complex (MHC) comprises related gene families, some of which are highly polymorphic, whose protein products mediate immune response. Rhesus macaques (Macaca mulatta) are a vital animal model for research in human diseases and are native to regions extending from Afghanistan in the west to the Eastern Plains of China and from Peking to the north, southward through islands of Southeast Asia. The distributions of MHC class-II Mamu DQA1 and Mamu DQB1 alleles in two groups of domestically bred rhesus macaques of Indian and Chinese origin and the Mamu DQA1 genotypes of a small number of Burmese rhesus macaques were compared. Major allelic differences were observed between the Indian and Chinese rhesus macaques, and gene diversity decreased from east to west. These and other intra-specific genetic differences among regional populations of rhesus macaques might influence the outcome of biomedical research in which they are used as subjects, and illustrate the importance of completely genetically characterizing subjects used as animal models in biomedical research.     

Electrical impedance measurements in the arm and the leg during a thirty day bed rest study

The need to detect, follow and understand the effects of gravity on body fluid distribution is a constant stimulus to the quest for new techniques in this area of research. One of these techniques is electrical bioimpedance spectroscopy (BIS). Although not new, this is a technique whose applications to biomedical research are fairly recent. What is new is the development of instrumentation that has made practical the use of impedance spectroscopy in the biomedical setting, particularly in studies involving human subjects. The purpose of this paper is to report impedance spectroscopy observations made on a subject who was submitted to bed rest for a period of thirty days. These observations were made as part of a study on muscle atrophy during a thirty day head down bed rest. Since bed rest studies are very costly in human and financial terms, and technically difficult to realize, we felt that even though the present study deals only with a single case it was worthy of reporting because it illustrates kinds of questions impedance spectroscopy may help to answer in microgravity research.     

Distinguishing medical practice and research: the special case of IVF

The debate over the acceptability of human embryo research takes place within the context of a broader regulatory framework for experimentation with human subjects. Using the Australian situation for illustration, Gaze and Dawson examine the concepts of therapeutic, nontherapeutic, and destructive experimentation in medical practice. They explore the problems of applying these concepts to human embryo research by asking whether the embryo or the woman undergoing in vitro fertilization (IVF) treatment is the experimental subject. They argue that when the embryo is treated as the sole subject, the woman is lost sight of, and that research that is therapeutic for the embryo may be nontherapeutic for her. Regulation of embryo research should take into account the relationship between research and the woman's treatment, the dependence of embryos upon women for gestation, and the empirical, uncertain nature of biomedical knowledge.     

Biomedical Scientists' Perceptions of Ethical and Social Implications: Is There a Role for Research Ethics Consultation?

Background

Research ethics consultation programs are being established with a goal of addressing the ethical, societal, and policy considerations associated with biomedical research. A number of these programs are modelled after clinical ethics consultation services that began to be institutionalized in the 1980s. Our objective was to determine biomedical science researchers'' perceived need for and utility of research ethics consultation, through examination of their perceptions of whether they and their institutions faced ethical, social or policy issues (outside those mandated by regulation) and examination of willingness to seek advice in addressing these issues. We conducted telephone interviews and focus groups in 2006 with researchers from Stanford University and a mailed survey in December 2006 to 7 research universities in the U.S.

Findings

A total of 16 researchers were interviewed (75% response rate), 29 participated in focus groups, and 856 responded to the survey (50% response rate). Approximately half of researchers surveyed (51%) reported that they would find a research ethics consultation service at their institution moderately, very or extremely useful, while over a third (36%) reported that such a service would be useful to them personally. Respondents conducting human subjects research were more likely to find such a service very to extremely useful to them personally than respondents not conducting human subjects research (20% vs 10%; chi² p<0.001).

Conclusion

Our findings indicate that biomedical researchers do encounter and anticipate encountering ethical and societal questions and concerns and a substantial proportion, especially clinical researchers, would likely use a consultation service if they were aware of it. These findings provide data to inform the development of such consultation programs in general.     

Preparing chimpanzees for laboratory research

The chimpanzee is the only representative of the Great Apes that is extensively involved in biomedical research in primate laboratories. These apes are used as animal models in a variety of studies, including research on infectious disease, parasitic disease, pharmacokinetic studies, neuroscience, cognition, and behavior. Chimpanzees used in biomedical research in the United States reside largely in six specialized research and holding facilities, and most of the research with them is conducted at these sites. Given the relatively small population of chimpanzees and its importance to biomedical research, it is imperative that we carefully manage the care, production, and use of these animals in biomedical research studies. Selection criteria and preparation techniques are reviewed in this article in an effort to begin a discussion on best practices for choosing and handling chimpanzees participating in biomedical research. The use of routine health assessment information is described for subject selection, as are behavioral issues to be considered. Due to the relatively small number of chimpanzees available, issues related to experimental design and multiple uses of chimpanzees are discussed. Practices related to the transportation and acclimation of chimpanzees are described. Finally, behavioral conditioning procedures are discussed, including habituation, desensitization, and positive reinforcement training that have been applied to reduce animal distress and improve the quality of the science being conducted with chimpanzee subjects.     

High-tech biomedical research: lessons from Iran's experience

Iran has recently made a significant progress in the field of biomedical science and launched an appreciable number of new high-tech biomedical research projects. Review of Iran's experience in advancing its biomedical research and the pitfalls the country encountered during the years of its progress could be of interest to other countries with similar technological conditions. As needs assessment and human resources have pivotal roles in any research infrastructure, here, we have delineated these factors and explored ways by which optimum advantage could be gained from them.     

Future of biobanking in microbiology for medical research.

Biobanks are actively contributing to advances in biomedical research by offering opportunities to link laboratory research with clinical applications and by accelerating developments in personalized medicine. Microbiologists have a long tradition of storing microorganisms as part of projects focused on microbial genetics or phenotypic investigations. However, the impressive recent advances of biomedical translational research demand the integration of biobanks with high-level technological infrastructures in genomics, proteomics, bioinformatics, patient information systems and disease registries, where data originating from microorganisms are linked with human clinical information with the ultimate aim of improving healthcare by increasing the quality of biomedical research.     

The emergence of biomedical anthropology and its implications for the future

Primarily during the past 15 years a distinct new area within physical anthropology has emerged, biomedical anthropology. Physical anthropologists have become heavily involved in studying problems of relevance to the health and illness patterns of living humans. There has been a proportionate increase in biomedically focused papers published in the American Journal of Physical Anthropology, in biomedically focused papers presented at annual meetings of the American Association of Physical Anthropologists, and in physical anthropology doctoral dissertations oriented toward modern biomedical phenomena. Proportionately more physical anthropologists are now employed in medical schools and there has been recent growth in the proportion of physical anthropologists in anthropology departments who claim some aspect of biomedical anthropology as a research interest. Increasingly, physical anthropologists are focusing their research on cardiovascular disease, the leading cause of death in America. These distinct trends are partially a result of the nature of physical anthropology and its unique biocultural perspective. However the growth of applied anthropology, the present academic marketplace, and the availability of research funds are probably also contributing factors. The emergency of biomedical anthropology holds promise for the future of physical anthropology and for its current employment crisis. Careers with academic and nonacademic organizations engaged in biomedical research appear to be a viable alternative to careers in departments of anthropology, for biomedical anthropologists. This will entail some reorientation of graduate training for physical anthropologists. More emphasis will have to be placed on substantive biomedical subjects, research methods, and data management and analysis.     

Categorization of humans in biomedical research: genes,race and disease

A debate has arisen regarding the validity of racial/ethnic categories for biomedical and genetic research. Some claim 'no biological basis for race' while others advocate a 'race-neutral' approach, using genetic clustering rather than self-identified ethnicity for human genetic categorization. We provide an epidemiologic perspective on the issue of human categorization in biomedical and genetic research that strongly supports the continued use of self-identified race and ethnicity.     

Defending the social value of knowledge as a safeguard for public trust

The ‘socially valuable knowledge’ (SVK) principle has been widely acknowledged as one of the most important guiding principles for biomedical research involving human subjects. The principle states that the potential of producing socially valuable knowledge is a necessary requirement, although not sufficient, for the ethical conduct of research projects. This is due to the assumption that the social value of knowledge avoids exploitation of research subjects and justifies the use of health resources. However, more recently, several authors have started interrogating the validity of SVK in research and offered various lines of argument against the SVK principle as a necessary constraint to research. In this article, I will reconstruct the main arguments of this discussion between defenders and debunkers of the SVK principle and offer a third way to consider the social value of knowledge in research studies. I will argue that the social value of knowledge can be supported by an independent justification. This justification of the SVK principle addresses the rationality and common interest of researchers. Thus, I will introduce the SVK principle as a safeguarding principle for public trust based on a conceptual framework by Alex John London. My approach justifies keeping the principle as a precautionary and rational requirement for human health research that all rational stakeholders can agree upon.     

转基因家兔模型制作方法

作为生物医学研究重要的实验动物模型,转基因家兔已经被广泛应用在人类心脑血管疾病、艾滋病以及癌症等生物医学研究领域,特别是利用转基因家兔模型在人类动脉粥样硬化实验研究中已经取得了令人注目的成绩。本文结合我们自己制作转基因家兔的经验、研究成果以及文献资料,详细介绍了利用原核显微注射法、直接将外源基因注入受精卵雄原核中的转基因家兔制作技术,回顾了利用转基因家兔模型在生物医学研究中取得的重要进展。     

Fourth meeting of the European Network of Research Tissue Banks – Future strategy to increase collaborations in the supply of human tissue for biomedical research

This report records the Fourth meeting of the European Network of Research Tissue Bank (Brussels, 18th March 2004) which was attended by Mel Read MEP. The existing membership of this informal group represents European Human Research Tissue Bankers, biomedical researchers seeking access to human tissue and allied groups including animal welfare representatives. This Fourth meeting provided a forum to update members on individual activity in this area. A particular focus of this meeting was to consider the status of this group and future affiliations to increase the profile and activity of this Network. This meeting addressed differences in legislative and ethical requirements governing the use of human tissue in biomedical research in the different countries represented. Future activity of the ENRTB, planned at this meeting, will target harmonisation of current differences which are currently barriers to increased access to human tissue for biomedical research. Through the harmonisation of procurement, processing and distribution of human tissue specimens the ENRTB will provide a mechanism to benefit human health through increased use of human tissue in pharmacotoxicological studies and the associated replacement of animal tests.     

Nonhuman primate transgenesis: progress and prospects

The nonhuman primate is used extensively in biomedical research owing to its close similarities to human physiology and human disease pathophysiology. Recently, several groups have initiated efforts to genetically manipulate nonhuman primates to address complex questions concerning primate-specific development and physiological adaptation. Primates pose unique challenges to transgenesis and, although this field is still in its infancy, the potential for obtaining new insights into primate physiology and gene function is unprecedented. This review focuses on the methods and potential applications of genetically altered nonhuman primates in biomedical research.     

Advantages and limitations of nonhuman primates as animal models in genetic research on complex diseases

Abstract: The genetic similarity between humans and nonhuman primates makes nonhuman primates uniquely suited as models for genetic research on complex physiological and behavioral phenotypes. By comparison with human subjects, nonhuman primates, like other animal models, have several advantages for these types of studies: 1) constant environmental conditions can be maintained over long periods of time, greatly increasing the power to detect genetic effects; 2) different environmental conditions can be imposed sequentially on individuals to characterize genotype-environment interactions; 3) complex pedigrees that are much more powerful for genetic analysis than typically available human pedigrees can be generated; 4) genetic hypotheses can be tested prospectively by selective matings; and 5) essential invasive and terminal experiments can be conducted. Limitations of genetic research with nonhuman primates include cost and availability. However, the ability to manipulate both genetic and environmental factors in captive primate populations indicates the promise of genetic research with these important animal models for illuminating complex disease processes. The utility of nonhuman primates for biomedical research on human health problems is illustrated by examples concerning the use of baboons in studies of osteoporosis, alcohol metabolism, and lipoproteins.