Human genome research and the public interest: progress notes from an American science policy experiment.

This essay reviews the efforts of the U.S. Human Genome Project to anticipate and address the ethical, legal, and social implications of new advances in human genetics. Since 1990, approximately $10 million has been awarded by the National Institutes of Health and the Department of Energy, in support of 65 research, education, and public discussion projects. These projects address four major areas of need: (1) the need for both client-centered assessments of new genetic services and for improved knowledge of the psychosocial and ethnocultural factors that shape clients' clinical genetic experiences; (2) the need for clear professional policies regarding human-subject research, clinical practice standards, and public health goals in human genetics; (3) the need for social policy protection against unfair access to and use of personal genetic information; and (4) the need for improved public and professional understanding and discussion of these issues. The Human Genome Project's goal is to have defined, by 1995, policy options and programs capable of addressing these needs.     

Ethical issues and GenomEUtwin.

The post-genomic era is witnessing a proliferation of large-scale and population based genetic and genomic research projects. Many countries have or are establishing research biobanks and, as with GenomEUtwin, there is great interest in building multinational projects that link genotypic and phenotypic information from different centers. Clearly, the conduct of these projects raises multiple ethical issues, and the knowledge generated will continually recast the ethical, legal and social implications (ELSI) of such research. Maximising the scientific profit from this work while minimizing the risks to the participants requires full integration of ethics components into the structure and functioning of these projects. GenomEUtwin is organized around five intellectual cores, including an Ethics Core which operates across the entire project. This paper describes the role of the Ethics Core and presents an overview of the guidelines on which the principles followed in GenomEUtwin are based. We outline the major ethical concerns of our project and highlight complexities arising from diverse national legislations. Finally, the role of empirically based ethics research is discussed for understanding the ethical, legal, social and economic implications of human genetics and genomics research.     

Society and ethics - the genetics of disease

Established guidance for the protection of human subjects in research has provided the framework for research and clinical practice in genetics. Three key principles to emerge are the requirements for consent, privacy and confidentiality. However, recent research on genetic susceptibility to common diseases indicates that it may be more difficult to decide if and when genetic testing will be appropriate. Risks of disease may be low and interventions may not be available. Today, debate is primarily focussed on ethical issues raised by the use and storage of genetic information. One of the earliest experiences of genetic testing for some people is likely to be in the area of pharmacogenetics. Debate about ethical issues has been focused on the implications of patient stratification, particularly with regard to the availability of medicines for small groups and the significance of racial variation in response to medicines. The possible use of personal genetic information by insurance companies and employers has also been an issue that legislators have taken seriously.     

Tailored Medicine: Whom Will it Fit? The Ethics of Patient and Disease Stratification

A key selling point of pharmacogenetics is the genetic stratification of either patients or diseases in order to target the prescribing of medicine. The hope is that genetically 'tailored' medicines will replace the current 'one-size-fits-all' paradigm of drug development and usage. This paper is concerned with the relationship between difference and justice in the use of pharmacogenetics. This new technology, which facilitates the identification and use of difference, has, we shall argue, the potential to lead to injustice either by the inappropriate use of difference or through the inappropriate failure to use difference. We build on empirical data from a detailed study of the range of options for the development of pharmacogenetics to present a consideration of the ethical issues that surround patient and disease stratification. In it we explore the ways in which the use of pharmacogenetics may lead to the creation of new, genetically stratified, forms of difference and new forms of injustice based on these divisions. We also examine the ways in which existing forms of difference and social stratification may interact with the use of pharmacogenetics. In conclusion, we suggest how an understanding of these ethical issues could usefully inform future policy discussions.     

A Brief History of Biomedical Research Ethics in Iran: Conflict of Paradigms

During the past two decades, Iran has experienced a noteworthy growth in its biomedical research sector. At the same time, ethical concerns and debates resulting from this burgeoning enterprise has led to increasing attention paid to biomedical ethics. In Iran, Biomedical research ethics and research oversight passed through major periods during the past decades, separated by a paradigm shift. Period 1, starting from the early 1970s, is characterized by research paternalism and complete reliance on researchers as virtuous and caring physicians. This approach was in concordance with the paternalistic clinical practice of physicians outside of research settings during the same period. Period 2, starting from the late 1990s, was partly due to revealing of ethical flaws that occurred in biomedical research in Iran. The regulatory and funding bodies concluded that it was not sufficient to rely solely on the personal and professional virtues of researchers to safeguard human subjects' rights and welfare. The necessity for independent oversight, emphasized by international declarations, became obvious and undeniable. This paradigm shift led to the establishment of research ethics committees throughout the country, the establishment of academic research centers focusing on medical ethics (MEHR) and the compilation of the first set of national ethical guidelines on biomedical research–one of the first and most important projects conducted by and in the MEHR. Although not yet arrived, ‘period 3’ is on its way. It is predictable from the obvious trends toward performance of high‐quality clinical research and the appearance of a highly educated new generation, especially among women.     

CONTEMPORARY MEDICAL ETHICS: AN OVERVIEW FROM IRAN

The growing potential of biomedical technologies has increasingly been associated with discussions surrounding the ethical aspects of the new technologies in different societies. Advances in genetics, stem cell research and organ transplantation are some of the medical issues that have raised important ethical and social issues. Special attention has been paid towards moral ethics in Islam and medical and religious professions in Iran have voiced the requirement for an emphasis on ethics. In the last decade, great strides have been made in biomedical ethics, especially in the field of education, research and legislation. In this article, contemporary medical ethics in Iran, and the related moral philosophy, have been reviewed in brief and we have discussed some of the activities in the field of medical ethics that have been carried out in our country within recent years. These activities have included the establishment of the National and Regional Committees for Medical Research Ethics and the production of national codes of ethics in biomedical research in the 1990s and the introduction of a comprehensive strategic plan for medical ethics at the national level in 2002. This paper will discuss these issues, along with the production, in 2005, of the Specific National Ethical Guidelines for Biomedical Research.     

The ethical landscape of gene drive research

Gene drive technology has immense potential. The ability to bypass the laws of Mendelian inheritance and almost ensure the transmission of specific genetic material to future generations creates boundless possibilities. But alongside these boundless possibilities are major social and ethical issues. This article aims to introduce gene drive technology, some of its potential applications, and some of the social and ethical issues that arise during research into the technology. For example, is investigation into gene drives hubristic? Would applications of gene drives count as technological fixes? Or does research into such a technology sit on a slippery slope or lock us in to its full‐scale use? Are there perverse effects of engaging in research, and, most importantly, who ought to be included in the decision‐making process regarding research and field trials? Understanding the basic ethical landscape of this technology will prove invaluable to the public, scientists, and policy‐makers as research moves forward.     

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.     

Context, ethics and pharmacogenetics

Most of the literature on pharmacogenetics assumes that the main problems in implementing the technology will be institutional ones (due to funding or regulation) and that although it involves genetic testing, the ethical issues involved in pharmacogenetics are different from, even less than, 'traditional' genetic testing. Very little attention has been paid to how clinicians will accept this technology, their attitudes towards it and how it will affect clinical practice. This paper presents results from interviews with clinicians who are beginning to use pharmacogenetics and explores how they view the ethics of pharmacogenetic testing, its use to exclude some patients from treatment, and how this kind of testing fits into broader debates around genetics. In particular this paper examines the attitudes of breast cancer and Alzheimer's disease specialists. The results of these interviews will be compared with the picture of pharmacogenetics painted in the published literature, as a way of rooting this somewhat speculative writing in clinical practice.     

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.     

Pharmacogenetics: the bioethical problem of DNA investment banking

Concern about the ethics of clinical drug trials research on patients and healthy volunteers has been the subject of significant ethical analysis and policy development--protocols are reviewed by Research Ethics Committees and subjects are protected by informed consent procedures. More recently attention has begun to be focused on DNA banking for clinical and pharmacogenetics research. It is, however, surprising how little attention has been paid to the commercial nature of such research, or the unique issues that present when subjects are asked to consent to the storage of biological samples. Our contention is that in the context of pharmacogenetic add-on studies to clinical drug trials, the doctrine of informed consent fails to cover the broader range of social and ethical issues. Applying a sociological perspective, we foreground issues of patient/subject participation or 'work', the ambiguity of research subject altruism, and the divided loyalties facing many physicians conducting clinical research. By demonstrating the complexity of patient and physician involvement in clinical drug trials, we argue for more comprehensive ethical review and oversight that moves beyond reliance on informed consent to incorporate understandings of the social, political and cultural elements that underpin the diversity of ethical issues arising in the research context.     

Admixture mapping: from paradigms of race and ethnicity to population history

Admixture mapping is a whole genome association strategy that takes advantage of population history-or genetic ancestry-to map genes for complex diseases. However, because it uses racial/ethnic groupings to examine differential disease risk, admixture mapping raises ethical and social concerns. While there has been much theoretical commentary regarding the ethical and social implications of population-based genetic research, empirical data from stakeholders most closely involved with these studies is limited. One of the first admixture mapping studies carried out was a scan for Multiple Sclerosis (MS) risk factors in an African-American population. Applying qualitative research methods, we used this example to explore developing views, experiences and perceptions of the ethical and social implications of admixture mapping and other population-based research-their value, risks and benefits, and the future prospects of the field. Additionally, we sought to understand how social and ethical risks might be mitigated, and the benefits of this research optimized. We draw on in-depth, one-on-one interviews with leading population geneticists, genome scientists, bioethicists, and African-Americans with MS. Here we present our findings from this unique group of key informants and stakeholders.     

Ethics and biomedical research

Ethics in biomedical research took off from the 1947 Nuremberg Code to its own right in the wake of the Declaration of Helsinki in 1964. Since then, (inter)national regulations and guidelines providing a framework for clinical studies and protection for study participants have been drafted and implemented, while ethics committees and drug evaluation agencies have sprung up throughout the world. These two developments were crucial in bringing about the protection of rights and safety of the participants and harmonization of the conduct of biomedical research. Ethics committees and drug evaluation agencies deliver ethical and scientific assessments on the quality and safety of the projects submitted to them and issue respectively approvals and authorizations to carry out clinical trials, while ensuring that they comply with regulatory requirements, ethical principles, and scientific guidelines. The advent of biomedical ethics, together with the responsible commitment of clinical investigators and of the pharmaceutical industry, has guaranteed respect for the patient, for whom and with whom research is conducted. Just as importantly, it has also ensured that patients reap the benefit of what is the primary objective of biomedical research: greater life expectancy, well-being, and quality of life.     

Challenges Faced by Behavioral Genetic Studies: Researchers Perspective from the MENA Region

BackgroundBehavioral genetic studies are important for the understanding of the contribution of genetic variations to human behavior. However, such studies might be associated with some ethical concerns.MethodsIn the current study, ethical challenges related to studies of genetic variations contributing to human behavior were examined among researchers. To achieve the study purpose, the Middle East and North Africa (MENA) region researchers were taken as an example, where the after- mentioned ethical challenges were discussed among a group of researchers, who were the participants of an online forum. Discussions and responses of the participants were monitored and were later qualitatively analyzed.ResultsDiscussions revealed that several ethical challenges, including subjects’ recruitment, the difficulty of obtaining informed consents, and issues of privacy and confidentiality of obtained data as information leakage, in this case, will lead to social stigma and isolation of the participants and their immediate family members. Jordanian social and cultural norms, faith, and the tribal nature of the population were raised as a major challenge that might face conducting behavioral genetic studies in the Arab populations of the MENA. The lack of regulation related to the conduction of genetic studies, misunderstanding, and misuse of genetic information are other challenges. A full explanation of genetic research and the current and future possible benefits/risks of such research could be potential solutions.ConclusionIn conclusion, the MENA populations are tackled with major challenges in relation to conducting research studies in genetics/antisocial behavior field/s. Establishment of guidelines related to genetic studies, capacity building, increasing public awareness about the importance of genetic testing, and enhancing responsible conduct of research will facilitate the conduct of such sensitive studies in the future in the region.     

NUCEL (Cell and Molecular Therapy Center): A Multidisciplinary Center for Translational Research in Brazil

Social and economical development is closely associated with technological innovation and a well-developed biotechnological industry. In the last few years, Brazil’s scientific production has been steadily increasing; however, the number of patents is lagging behind, with technological and translational research requiring governmental incentive and reinforcement. The Cell and Molecular Therapy Center (NUCEL) was created to develop activities in the translational research field, addressing concrete problems found in biomedical and veterinary areas and actively searching for solutions by employing a genetic engineering approach to generate cell lines over-expressing recombinant proteins to be transferred to local biotech companies, aiming at furthering the development of a national competence for local production of biopharmaceuticals of widespread use and of life-saving importance. To this end, mammalian cell engineering technologies were used to generate cell lines over-expressing several different recombinant proteins of biomedical and biotechnological interest, namely, recombinant human Amylin/IAPP for diabetes treatment, human FVIII and FIX clotting factors for hemophilia, human and bovine FSH for fertility and reproduction, and human bone repair proteins (BMPs). Expression of some of these proteins is also being sought with the baculovirus/insect cell system (BEVS) which, in many cases, is able to deliver high-yield production of recombinant proteins with biological activity comparable to that of mammalian systems, but in a much more cost-effective manner. Transfer of some of these recombinant products to local Biotech companies has been pursued by taking advantage of the São Paulo State Foundation (FAPESP) and Federal Government (FINEP, CNPq) incentives for joint Research Development and Innovation partnership projects.     

A human rights approach to an international code of conduct for genomic and clinical data sharing

Fostering data sharing is a scientific and ethical imperative. Health gains can be achieved more comprehensively and quickly by combining large, information-rich datasets from across conventionally siloed disciplines and geographic areas. While collaboration for data sharing is increasingly embraced by policymakers and the international biomedical community, we lack a common ethical and legal framework to connect regulators, funders, consortia, and research projects so as to facilitate genomic and clinical data linkage, global science collaboration, and responsible research conduct. Governance tools can be used to responsibly steer the sharing of data for proper stewardship of research discovery, genomics research resources, and their clinical applications. In this article, we propose that an international code of conduct be designed to enable global genomic and clinical data sharing for biomedical research. To give this proposed code universal application and accountability, however, we propose to position it within a human rights framework. This proposition is not without precedent: international treaties have long recognized that everyone has a right to the benefits of scientific progress and its applications, and a right to the protection of the moral and material interests resulting from scientific productions. It is time to apply these twin rights to internationally collaborative genomic and clinical data sharing.     

Advances in pharmacogenomic research and development

Technological achievements in the last 5 to 10 yr and their application to sequencing and polymorphism discovery in the human genome have fostered a renewed interest in the genetic basis of drug response. Consequently, the field of pharmacogenetics/pharmacogenomics has been gaining momentum, fueled not only on technology but also on results of empirical studies of the human genome and on genetic epidemiology studies of real drugs in patient populations. This review discusses some of the recent advances in pharmacogenomic research and development over the last few years that include understanding the architecture of the human genome, the creation of population deoxyribonucleic acid (DNA)/data banks, assessment of the clinical validity of genetic markers, and experience with regulatory aspects of pharmacogenomics.     

The Disclosure of Genetic Information: A Human Research Ethics Perspective

Increasing emphasis on genetic research means that growing numbers of human research projects in Australia will involve complex issues related to genetic privacy, familial information and genetic epidemiology. The Office of Population Health Genomics (Department of Health, Western Australia) hosted an interactive workshop to explore the ethical issues involved in the disclosure of genetic information, where researchers and members of human research ethics committees (HRECs) were asked to consider several case studies from an ethical perspective. Workshop participants used a variety of approaches to examine the complex ethical issues encountered, but did not consistently refer to the values and principles outlined in the National Statement on Ethical Conduct in Human Research (NHMRC 2007) or apply rational ethical approaches. Overall, the data suggested that both researchers and HREC members may benefit from further education and support regarding the application of ethical frameworks to the issues encountered in genetic research.     

基于灰色综合关联分析法的粤港澳大湾区生物医药产业效益研究*

生物医药产业是中国医药制造业的第三大产业,也是粤港澳大湾区重点扶持的新兴高技术产业之一。透视产业主营业务收入与各类指标的关联情况是进一步指导粤港澳大湾区生物医药产业建设规划的必要之举。而灰色综合关联分析法是探索指标间关联程度的重要工具。通过多种权威途径获得粤港澳大湾区生物医药产业规模以上企业数量、企业孵化器数量、新增专利数、自然科学基金立项投入总额、非自然科学基金立项数量、产学研合作项数量六大指标数据。采用灰色关联分析法,将所得数据进行建模并求解,得出这六大指标与粤港澳大湾区生物医药产业主营业务收入的关联度。结果显示,规模以上企业数量与粤港澳大湾区生物医药产业主营业务收入的关联度最高,其次为自然科学基金立项投入总额,再次为产学研合作项数量,非自然科学基金立项数量位列第四,企业孵化器数量、新增专利数分别位列第五、第六。因此,谋求粤港澳大湾区生物医药产业的进一步发展应着重从提高规模以上企业数量、重视自然科学基金投入、加强政产学研合作3个层面入手。