Using human samples in proteomics-based drug development: bioethical aspects

Human samples and related medical data are expected to play an elevated role in application-based biomedical proteomics research. Against this framework, some facts should be kept in mind by academic and industrial researchers: international framework conditions on the use of human samples for research purposes are heterogeneous. For example, the value added by the use of human samples for product development is significant and the patient's personal and property rights may be affected. The body of national laws is growing and these laws are binding; guidelines published by international organizations should be respected. The most important aspect regards the informed consent of the patient, which is addressed in detail.     

Ethical and regulatory issues arising from proteomic research and technology

Over the last two decades, medical research has begun to make extensive use of products of human origin in therapeutics, oncology, and most recently, in genetic diseases. This has raised many ethical issues involving patient rights, including issues of consent. Besides informed consent, researchers should address several topics when designing studies using human tissues. Reward for the patient should be kept minimal. Sample transfer should be organized along non-profit lines, at least in Europe. Sampling procedures should be at no risk for human volunteers, and at minimal risk for patients. Biosafety aspects should be addressed, in particular when international collaborations are intended or when collaboration is existing between academia and industry. Regulations on importation and exportation of human tissues should be observed. Data acquisition and storage should be addressed in accordance with national data protection regulations, in particular when using computerized databases. If follow-up information is to be taken, the authorization for such information should be requested. The right for patient's information (or for no information) on the research results should also be addressed. The issues of validation and patenting should be also solved, usually by informing the patient that he/she will have no commercial rights on potential research results. The patient should be told if the samples are transferred to another research laboratory or private company. Samples and related data should be destroyed on request at any time point during the course of the study. If possible, traceability of the donor should be ensured.     

Biobanking residual tissues

Health-care research relies largely on human materials stored in highly specialised biorepositories. Medical translational research on tissues can be performed using a variety of resources in distinct situations. The best known is the secondary use of pathology archives where paraffin-embedded tissues are stored for diagnostic reasons. Another is collecting and storing frozen material obtained from leftover surgical diagnosis. Such residual tissues can either be used directly in research projects or used in the context of a clinical trial with new interventional medicinal products. The latter can make the regulations governing the use of these materials for medical research much more complicated. The use of residual materials is very distinct from biobanking projects for which tissue is specifically collected. This article describes the consequences of using residual human material from different sources in distinct situations and why signed informed consent is not always the preferred choice of individual countries regarding the use of residual material. In addition, signed informed consent is overdone when using residual tissues in medical research. We maintain that the opt-out system is a balanced choice if certain requirements are met, relating to sufficient transparency about using residual tissue for research, the purpose of such research and to the confidentiality of the data used in that research. Finally, the international exchange of samples can be based on the laws and regulations of the countries of origin. Respecting these form the basis of what can and cannot be done in the country where the research on the samples is being performed.     

CRISPR Ethics: Moral Considerations for Applications of a Powerful Tool

With the emergence of CRISPR technology, targeted editing of a wide variety of genomes is no longer an abstract hypothetical, but occurs regularly. As application areas of CRISPR are exceeding beyond research and biomedical therapies, new and existing ethical concerns abound throughout the global community about the appropriate scope of the systems' use. Here we review fundamental ethical issues including the following: 1) the extent to which CRISPR use should be permitted; 2) access to CRISPR applications; 3) whether a regulatory framework(s) for clinical research involving human subjects might accommodate all types of human genome editing, including editing of the germline; and 4) whether international regulations governing inappropriate CRISPR utilization should be crafted and publicized. We conclude that moral decision making should evolve as the science of genomic engineering advances and hold that it would be reasonable for national and supranational legislatures to consider evidence-based regulation of certain CRISPR applications for the betterment of human health and progress.     

Informed consent,and an ethico- legal framework for paediatric observational research and biobanking: the experience of an Italian birth cohort study

Birth cohort studies are important tools for life-course epidemiology, given the spectrum of the environmental, behavioural, and genetic factors that should be considered when making judgements on human health. Biobanks are valuable components of studies designed to investigate the genetic variability of diseases and improve phenotypic characterisation. In studies involving vulnerable populations and biobanks, it is essential to provide ethical reasoning and analyse the legal requirements. We describe the processes and the tools used in the iterative design of an appropriate informed consent model and the ethico-legal framework of the Piccolipiù study. The Piccolipiù study is a prospective population-based study funded by the Italian Ministry of Health that intends to enrol 3,000 newborns and their mothers in five Italian cities, and to store biological samples for future use. To realise these objectives, we performed a thorough evaluation of the literature, of national and international guidelines, and of the impact of the Italian legal requirements for research biobanking. Discussions among stakeholders facilitated the design of the informed consent and the ethico-legal framework. Several topics are addressed, including the suitability of a broad informed consent for paediatric biobanks, infant vulnerability, access to and sharing of data, and the disclosure of individual’s genetic results. Discussion of the ethical and legal procedures adopted in epidemiological biobanking might be a fruitful ground for comparison both at the national level, where standardization and homogeneity are lacking, and at the international level, where different regulatory issues are often in the background and might hamper research biobanks networking.     

“野生动物”的概念框架和术语定义

“野生动物”(wild animal)一词不止在我国, 在全球的英语使用者中也有不同的含义。通过梳理相关研究、国内法和国际法背景下的定义和适用范围, 结合人类对动物繁殖和生活条件的控制情况, 本文提出了“野生动物”的二维概念框架, 梳理了动物从“野生”到“驯化”的12个连续状态。以下状态即未经中长期人工选择的动物类群应被视为野生动物: (1)其在荒野自然或人工环境(如城市或乡村)中自由生存繁殖, 无论是否存在人工投喂、经救护或辅助生殖后被放归的个体; (2)被捕捉圈养在人工环境中生活, 或源自野外但在圈养条件下出生的个体; (3)直系血亲(《濒危野生动植物种国际贸易公约》解释为世系前四代)仍有野外来源的人工繁育后代; (4)放生、逃逸或引入到自然环境中的人工繁育个体。在野生动物物种保护的目标和语境之下, 经过长期人工选择的驯化动物, 无论其是否在人类控制下生活, 如家养猫狗、家禽家畜或模式实验动物, 以及流浪猫狗、放生禽畜和野化家养动物等都不是“野生动物”。但对于一些经过一定程度的人工选择, 所处人类控制情况和对野外种群的影响各异(如经过多代人工繁育的驯养动物、因人类活动导致的外来动物等), 其是否需被作为野生动物管理, 则需要根据生态安全、物种管理、立法目标等特别设定监管范围。《中华人民共和国野生动物保护法》的保护对象可以考虑为: 受到人类威胁濒临灭绝的, 或者具有重要生态作用的野生动物物种, 其状态可不限于是在野外还是人工控制条件下。其他动物的管理, 可根据遗传资源保护、疫病防控、动物福利和生态安全等需要, 另外设立《动物福利法》《生物安全法》等, 并和已有的法律法规如《动物防疫法》《渔业法》等做好衔接。本文还就《野生动物保护法》可能采用的“野生动物”定义提出建议。     

Import and export of biological samples from tropical countries–considerations and guidelines for research teams

‘Biodiversity’ is increasingly perceived as an important resource for research and conservation, but also for economy. Conservation, access and sustainable use of biodiversity (genetic resources, species, samples) are negotiated on different political levels, resulting in an internationally binding legal framework. Resulting legislation is binding for all parties involved in biological sampling, i.e. researches and (and in italics) countries, and especially applies for tissue or DNA samples and dervied products thereof. Understanding and awareness of export and import permits for biological samples is increasingly important for biologists to perform research projects legally and timely. Nevertheless, some biologists are still exporting and importing biological samples ignoring or non-compliant with national and international legislation, conventions, and regulations. Resulting difficulties may not only cause serious problems during field work, but may also delay the export, import or exchange of samples. Comprehensive a priori information regarding legal requirements helps to avoid or at least diminish potential problems. We identified four major factors facilitating export/import permits: (1) good personal (mutually trusted) contacts in the country of origin, (2) understanding and compliance with all relevant laws and regulations; (3) access to information regarding knowledge on permits, regulations and laws including their circulation within the researcher communities; and (4) access to consistent and up to date regulations     

National interests and international collaboration: tensions and ambiguity among Finns towards usages of tissue samples

Recent trends in biobanking indicate that the practices associated with the collection and use of human tissue samples and related health information are increasingly becoming premised on networks of biobanks. These networks and partnerships often involve international collaborations, as well as public–private partnerships. This article reports on the results of a study of people's attitudes towards biobanking and the biomedical use of tissue samples in Finland. Three approaches were used to study these attitudes: a population-based survey, focus group interviews among members of patient organizations and short interviews with research participants. In particular, we look at the attitudes of respondents in these three studies towards the use of tissue samples and use them as a catalyst to discuss two dimensions of biomedical research: public/private and domestic/international. Our discussion highlights how notions of value related to the use of tissue samples vary and provide contrasting perspectives and ambiguity that people may have towards various types of research partnerships and the benefits that may arise from them.     

生物样本库及其伦理问题简介

随着分子和基因组信息对流行病学影响的增加,无数遗传流行病学研究和后人类基因组计划的研究都越来越依赖人类生物样本库的使用。生物样本库的范围也已横跨学术或者医院环境下的小数量收集到大规模的全国性储藏。尽管生物样本库的概念并不新,但是在基因组研究和后人类基因组计划的背景下,伴随它们十几年极大发展的是无数待解决的伦理挑战。从生物样本库的概念着手,介绍了其与一般遗传数据库的区别以及建立生物样本库的意义;然后介绍并比较国际上已有的生物样本库,以及其伦理问题和伦理法律框架的发展趋势。     

“2020年后全球生物多样性框架”的谈判进展以及对我国的建议

“2020年后全球生物多样性框架”是当前《生物多样性公约》谈判的焦点议题, 了解该议题的谈判进展将对我国顺利举办第15次缔约方大会(COP15)产生积极的作用。本文在梳理相关谈判进程的基础上, 分析了各方主要观点, 并就我国应对国际谈判并以东道国身份推进该框架的制定进程提出了建议。各方对制定框架的时间表、程序和一般性原则形成了较为一致的共识, 认为应尽快确定“2020年后全球生物多样性框架”的程序及时间表, 基于“爱知生物多样性目标”的执行经验、科学结论和和广泛的信息来源, 与“可持续发展目标”及其他国际进程衔接, 重视利用情景和模型, 并支持更多利益相关方参与制定过程。同时, 各方认为框架应主要包括土地利用、保护和恢复生物多样性的措施、解决生物多样性丧失的根本原因、主流化、能力建设、资源调动、国家承诺等要素。为应对国际谈判, 建议我国在《公约》谈判会议中适时提出以下观点: 重视实现可持续利用相关的目标; 提升评估指标体系的合理性; 科学制定措施。此外, 建议我国采取以下措施积极推进框架制定进程: 充分利用国际高级别会议, 提升政治重视程度; 积极与主要国际进程协作, 推进该框架深入讨论; 重视调动利益相关方积极性。     

International,interdisciplinary research in ecology: Some problems of organization and execution. The case of the man and the biosphere (MAB) programme

Ecological problems — because they involve interactions and interfaces — require for their solution a flexible, interdisciplinary approach. Ecological research can best be supported in an international, intergovernmental framework, but, at first sight, the requirements of such a framework may seem unwieldy to traditionally trained natural and social scientists. Experience acquired in implementing UNESCO's Man and the Biosphere (MAB) Programme indicates that it is possible to overcome the difficulties of conducting integrated research and to achieve internationally comparable results. The MAB Programme is a good example of both the potential and the limitations of integrated, international ecological research programs. There seem to be three imperatives for success: (1) research must be problem oriented, (2) the. unit selected for study must be sufficiently comprehensive and based on human use systems, and (3) research workers in various natural and social science disciplines and the administrative decision-makers must share responsibility for planning and execution.     

Sharing the benefits of genetic resources: from biodiversity to human genetics

Benefit sharing aims to achieve an equitable exchange between the granting of access to a genetic resource and the provision of compensation. The Convention on Biological Diversity (CBD), adopted at the 1992 Earth Summit in Rio de Janeiro, is the only international legal instrument setting out obligations for sharing the benefits derived from the use of biodiversity. The CBD excludes human genetic resources from its scope, however, this article considers whether it should be expanded to include those resources, so as to enable research subjects to claim a share of the benefits to be negotiated on a case-by-case basis. Our conclusion on this question is: 'No, the CBD should not be expanded to include human genetic resources.' There are essential differences between human and non-human genetic resources, and, in the context of research on humans, an essentially fair exchange model is already available between the health care industry and research subjects. Those who contribute to research should receive benefits in the form of accessible new health care products and services, suitable for local health needs and linked to economic prosperity (e.g. jobs). When this exchange model does not apply, as is often the case in developing countries, individually negotiated benefit sharing agreements between researchers and research subjects should not be used as 'window dressing'. Instead, national governments should focus their finances on the best economic investment they could make; the investment in population health and health research as outlined by the World Health Organization's Commission on Macroeconomics and Health; whilst international barriers to such spending need to be removed.     

A review of global instruments to combat invasive alien species in forestry

Although impacts of biological invasions may be local, at least at first, the causes of introduction are mostly international. Through trade and transport pathways, countries both send and receive non-native species. There are numerous international and regional instruments, binding and nonbinding, which have been developed to deal with the problem of the movement of alien invasive species, however there are gaps in the current international framework. Global goals in the management of forestry-related threats from invasive alien species should include making best use of existing regulatory frameworks, investing more into global research initiatives, and targeting existing tools and resources more effectively. Given the lack of resources for many developing countries to undertake research, conduct risk assessments and implement quarantine measures, there is a need for regional and global support for countries that lack sufficient resources to implement effective phytosanitary systems.     

Quality control of human tissues-experience from the Indiana University Cancer Center-Lilly Research Labs human tissue bank

The success of molecular research and its applications in both the clinical and basic research arenas is strongly dependent on the collection, handling, storage, and quality control of fresh human tissue samples. This tissue bank was set up to bank fresh surgically obtained human tissue using a Clinical Annotated Tissue Database (CATD) in order to capture the associated patient clinical data and demographics using a one way patient encryption scheme to protect patient identification. In this study, we determined that high quality of tissue samples is imperative for both genomic and proteomic molecular research. This paper also contains a brief compilation of the literature involved in the patient ethics, patient informed consent, patient de-identification, tissue collection, processing, and storage as well as basic molecular research generated from the tissue bank using good clinical practices. The current applicable rules, regulations, and guidelines for handling human tissues are briefly discussed. More than 6,610 cancer patients have been consented (97% of those that were contacted by the consenter) and 16,800 tissue specimens have been banked from these patients in 9 years. All samples collected in the bank were QC’d by a pathologist. Approximately 1,550 tissue samples have been requested for use in basic, clinical, and/or biomarker cancer research studies. Each tissue aliquot removed from the bank for a research study were evaluated by a second H&E, if the samples passed the QC, they were submitted for genomic and proteomic molecular analysis/study. Approximately 75% of samples evaluated were of high histologic quality and used for research studies. Since 2003, we changed the patient informed consent to allow the tissue bank to gather more patient clinical follow-up information. Ninety two percent of the patients (1,865 patients) signed the new informed consent form and agreed to be re-contacted for follow-up information on their disease state. In addition, eighty five percent of patients (1,584) agreed to be re-contacted to provide a biological fluid sample to be used for biomarker research.     

The Social Value of Knowledge and International Clinical Research

In light of the growth in the conduct of international clinical research in developing populations, this paper seeks to explore what is owed to developing world communities who host international clinical research. Although existing paradigms for assigning and assessing benefits to host communities offer valuable insight, I criticize their failure to distinguish between those benefits which can justify the conduct of research in a developing world setting and those which cannot. I argue that the justification for human subjects research is fundamentally grounded in the social value of knowledge, and that this value is context‐dependent in a manner which should inform our ethical evaluation of the conduct of research in specific settings. I propose a new framework for the assessment of research benefits assigned to developing world host communities, a natural implication of which is to limit the types of research projects which may permissibly be conducted in developing world settings.     

The Australian joint inquiry into the Protection of Human Genetic Information

The Australian Law Reform Commission (ALRC) and the Australian Health Ethics Committee are currently engaged in an inquiry into the Protection of Human Genetic Information. In particular, the Attorney-General and the Minister for Health and Ageing have asked us to focus, in relation to human genetic information and tissue samples, on how best to ensure world's best practice in relation to: privacy protection; protection against unlawful discrimination; and the maintenance of high ethical standards in medical research and clinical practice. While initial concerns and controversies have related mainly to aspects of medical research (e.g. consent; re-use of samples) and access to private insurance coverage, relevant issues arise in a wide variety of contexts, including: employment; medical practice; tissue banks and genetic databases; health administration; superannuation; access to government services (e.g. schools, nursing homes); law enforcement; and use by government authorities (e.g. for immigration purposes) or other bodies (e.g. by sports associations). Under the Australian federal system, it is also the case that laws and practices may vary across states and territories. For example, neonatal genetic testing is standard, but storage and retention policies for the resulting 'Guthrie cards' differ markedly. Similarly, some states have developed highly linked health information systems (e.g. incorporating hospitals, doctors' offices and public records), while others discourage such linkages owing to concerns about privacy. The challenge for Australia is to develop policies, standards and practices that promote the intelligent use of genetic information, while providing a level of security with which the community feels comfortable. The inquiry is presently reviewing the adequacy of existing laws and regulatory mechanisms, but recognizes that it will be even more important to develop a broad mix of strategies, such as community and professional education, and the development of official standards and industry codes that reflect emerging international best practice in the area.     

Alternatives of Informed Consent for Storage and Use of Human Biological Material for Research Purposes: Brazilian Regulation

Informed consent is recognized as a primary ethical requirement to conduct research involving humans. In the investigations with the use of human biological material, informed consent (IC) assumes a differentiated condition on account of the many future possibilities. This work presents suitable alternatives for IC regarding the storage and use of human biological material in research, according to new Brazilian regulations. Both norms – Resolution 441/11 of the National Health Council, approved on 12 May 2011, and Ordinance 2.201 (NATIONAL GUIDELINES FOR BIOREPOSITORIES AND BIOBANKS OF HUMAN BIOLOGICAL MATERIAL FOR RESEARCH PURPOSE) of the Brazil Ministry of Health, approved on 14 September 2011 – state that the consent of subjects for the collection, storage and use of samples stored in Biobanks is necessarily established by means of a Free and Informed Consent Form (ICF). In order to obtain individual and formal statements, this form should contain the following two mutually exclusive options: an explanation about the use of the stored material in each research study, and the need for new consent or the waiver thereof when the material is used for a new study. On the other hand, ICF suitable for Biorepositories must be exclusive and related to specific research. Although Brazilian and international regulations identify the main aspects to be included in the IC, efforts are still necessary to improve the consent process, so that the document will become a bond of trust between subject and researcher.     

Preface

Abstract

Major naval weapons and weapons systems are examined as they relate to naval strategy and the law of the sea. Although there are some legal limitations on the development and use of nuclear and other mass destruction weapons on the seabed, and in nuclear free zones such as Latin America, and on naval weaponry in Antarctica, the use of naval weapons systems is largely unrestricted by international law and the law of the sea. Weapons systems from mines to large submarines and carriers are related to areas, to categories of states, and to the main sub‐fields of international relations. The conclusion to be drawn is that a third Hague Conference on the laws of war should be called and arms control and disarmament issues in naval weaponry should be addressed urgently. Detailed data on naval weapons, missile systems, and maritime zones are presented in three appendixes. Glossary of Abbreviations for Naval Weaponry immediately precedes the appendices.     

Combining efficiency and concerns about integrity when using human biobanks

In the debate about human bio-sampling the interests of patients and other sample donors are believed to stand against the interests of scientists and of their freedom of research. Scientists want efficient access to and use of human biological samples. Patients and other donors of blood or tissue materials want protection of their integrity. This dichotomy is reflected in the Swedish law on biobanks, which came into effect 1 January 2003. In this article I argue that if the basic interest of scientists using human biological samples is in increasing knowledge and developing better treatments, and if the concept 'integrity' is properly understood, then sample donors should also be interested in promotion of efficiency as well as in the protection of their integrity. The basic premise of this argument is that donors of samples have interests related to the donation and use of samples as well as to the use of the results of the research, that is, new medical products and treatments. They have a role both as donors or participants in research and as end users of the research. I conclude that if (i) access to information acquired through biobank research is strictly limited to researchers, (ii) the information is protected by secrecy safeguards through coding and (iii) the procedures governing the research are open to public and democratic control, then most research using human biobanks may be carried out on the basis of making general information available when collecting biological samples, without further contact with participants.     

Addressing ethical issues in H3Africa research – the views of research ethics committee members

In June 2014, the H3Africa Working Group on Ethics organised a workshop with members of over 40 research ethics committees from across Africa to discuss the ethical challenges raised in H3Africa research, and to receive input on the proposed H3Africa governance framework. Prominent amongst a myriad of ethical issues raised by meeting participants were concerns over consent for future use of samples and data, the role of community engagement in large international collaborative projects, and particular features of the governance of sample sharing. This report describes these concerns in detail and will be informative to researchers wishing to conduct genomic research on diseases pertinent to the African research context.