Biomedical databases: protecting privacy and promoting research

When combined with medical information, large electronic databases of information that identify individuals provide superlative resources for genetic, epidemiology and other biomedical research. Such research resources increasingly need to balance the protection of privacy and confidentiality with the promotion of research. Models that do not allow the use of such individual-identifying information constrain research; models that involve commercial interests raise concerns about what type of access is acceptable. Researchers, individuals representing the public interest and those developing regulatory guidelines must be involved in an ongoing dialogue to identify practical models.     

Protection goals in environmental risk assessment: a practical approach

Policy protection goals are set up in most countries to minimise harm to the environment, humans and animals caused by human activities. Decisions on whether to approve new agricultural products, like pesticides or genetically modified (GM) crops, take into account these policy protection goals. To support decision-making, applications for approval of commercial uses of GM crops usually comprise an environmental risk assessment (ERA). These risk assessments are analytical tools, based on science, that follow a conceptual model that includes a problem formulation step where policy protection goals are considered. However, in most countries, risk assessors face major problems in that policy protection goals set in the legislation are stated in very broad terms and are too ambiguous to be directly applicable in ERAs. This means that risk assessors often have to interpret policy protection goals without clear guidance on what effects would be considered harmful. In this paper we propose a practical approach that may help risk assessors to translate policy protection goals into unambiguous (i.e., operational) protection goals and to establish relevant assessment endpoints and risk hypotheses that can be used in ERAs. Examples are provided to show how this approach can be applied to two areas of environmental concern relevant to the ERAs of GM crops.     

Ethical concerns regarding commercialization of deep brain stimulation for obsessive compulsive disorder

The United States Food and Drug Administration's recent approval of the commercial use of Deep Brain Stimulation (DBS) as a treatment for Obsessive Compulsive Disorder (OCD) will be discussed within the context of the existing USA regulatory framework. The purpose will be to illustrate the current lack of regulation and oversight of the DBS market, which has resulted in the violation of basic ethical norms. The discussion will focus on: 1) the lack of available evidence on procedural safety and efficacy, 2) the numerous conflicts of interest held by research investigators, and 3) the ambiguity of both aforementioned categories due to an inherent lack of transparency in the research. It is argued that in order to address these issues, ethical analyses of DBS for psychiatric disorders must include the role of the industry forces that have become the primary impetus for this research. As such, DBS for OCD serves as an important case example in studies of neurotechnology and innovative surgery.     

Antibodies in infectious diseases: polyclonals, monoclonals and niche biotechnology

Antibody preparations have a long history of providing protection from infectious diseases. Although antibodies remain the only natural host-derived defense mechanism capable of completely preventing infection, as products, they compete against inexpensive therapeutics such as antibiotics, small molecule inhibitors and active vaccines. The continued discovery in the monoclonal antibody (mAb) field of leads with broadened cross neutralization of viruses and demonstrable synergy of antibody with antibiotics for bacterial diseases, clearly show that innovation remains. The commercial success of mAbs in chronic disease has not been paralleled in infectious diseases for several reasons. Infectious disease immunotherapeutics are limited in scope as endemic diseases necessitate active vaccine development. Also, the complexity of these small markets draws the interest of niche companies rather than big pharmaceutical corporations. Lastly, the cost of goods for mAb therapeutics is inherently high for infectious agents due to the need for antibody cocktails, which better mimic polyclonal immunoglobulin preparations and prevent antigenic escape. In cases where vaccine or convalescent populations are available, current polyclonal hyperimmune immunoglobulin preparations (pIgG), with modern and highly efficient purification technology and standardized assays for potency, can make economic sense. Recent innovations to broaden the potency of mAb therapies, while reducing cost of production, are discussed herein. On the basis of centuries of effective use of Ab treatments, and with growing immunocompromised populations, the question is not whether antibodies have a bright future for infectious agents, but rather what formats are cost effective and generate safe and efficacious treatments to satisfy regulatory approval.     

Regulatory issues in aging pharmacology

Many current drugs increase the average lifespan by preventing fatal diseases or by slowing down the progressive degenerative diseases that increase mortality. The existing strategies and guidelines for the development and regulatory approval of new drugs are designed for such compounds. Rapid advances in understanding molecular mechanisms of aging make it possible to envisage future drugs that extend the lifespan by regulating aging mechanism outside of disease pathways. Strategies for development and regulatory approval of such drugs remain to be defined. Since the drug candidates will be given to healthy, elderly subjects, safety requirements will be extremely high. Clinical studies of many years' duration will be necessary to prove changes in longevity. These time intervals may exceed those of patent protection and thus minimize commercial incentives. Despite these challenges, two broadly defined pathways are feasible. First, it may be possible to obtain public funding for studies with voluntary participation of humans consuming existing drugs or natural compounds in the 'expected to be safe' category. Second, the development of novel drugs may proceed on the basis of well-defined biomarkers of aging that can serve as surrogate end points in clinical studies. The emerging approaches will prompt the regulatory agencies into taking the first steps towards regulatory guidance.     

The Happy Hen on Your Supermarket Shelf

This paper investigates what “free-range” eggs are available for sale in supermarkets in Australia, what “free-range” means on product labelling, and what alternative “free-range” offers to cage production. The paper concludes that most of the “free-range” eggs currently available in supermarkets do not address animal welfare, environmental sustainability, and public health concerns but, rather, seek to drive down consumer expectations of what these issues mean by balancing them against commercial interests. This suits both supermarkets and egg producers because it does not challenge dominant industrial-scale egg production and the profits associated with it. A serious approach to free-range would confront these arrangements, and this means it may be impossible to truthfully label many of the “free-range” eggs currently available in the dominant supermarkets as free-range.     

美、欧、日三国药物审批趋势解读（2004—2013 年）

2014 年5 月汤森路透集团的科学创新监管中心（CIRS）发表了一份“R&D Briefing 54”的报告。基于该报告对新活性物质的统计数据,分析美、欧、日三个药物审批机构,即美国食品与药品管理局、欧洲药物管理局和日本药品与医疗器械管理局的新药审批趋势。     

Therapeutic Fc-fusion proteins and peptides as successful alternatives to antibodies

Therapeutic antibodies have captured substantial attention due to the relatively high rate at which these products reach marketing approval, and the subsequent commercial success they frequently achieve. In the 2000s, a total of 20 antibodies (18 full-length IgG and 2 Fab) were approved by the Food and Drug Administration (FDA) or European Medicines Agency (EMA). In the 2010s to date, an additional 3 antibodies (denosumab, belimumab, ipilimumab) have been approved and one antibody-drug conjugate (brentuximab vedotin) is undergoing regulatory review and may be approved in the US by August 30, 2011. However, a less heralded group of antibody-based therapeutics comprising proteins or peptides fused with an Fc is following the success of classical antibodies.     

An economic evaluation of a genetic screening program for Tay-Sachs disease.

The resolution of policy questions relating to medical genetic screening programs will not be without considerable difficulty. Examples include such issues as the optimal degree of screening program expansion, the relative values of screening for different genetic diseases, the appropriate sources of program funding (public vs. private), and the relative value of funding expanded genetic screening programs vs. research directed toward elimination of genetic traits themselves. Information on the net impact of the relevant alternatives is greatly needed, and this need will increase if the National Genetics Act receives funding approval. We have provided what is hopefully a contribution toward this end. While our analysis pertains to a specific disease and a specific screening program for that disease, the methodology is readily generalizable to other genetic diseases, as well as programs of any size or structure. Hopefully, this will serve to stimulate further research efforts that we believe are needed for the objective consideration of resource allocation alternatives.     

基于不同利益相关者认知分析的生态移民安置区生态风险识别

生态移民安置区内,不同群体在生态环境保护方面存在复杂的利益冲突.基于安置区内利益群体对风险类别、干扰强度的识别,构建相应的决策模型,是生态移民安置区生态风险管理亟待解决的重要课题.本文依据利益相关者理论划分出生态移民安置区4类不同利益群体,并采用参与式半结构访谈法和定性聚合法,构建了3类一级变量和13个二级变量的生态风险因子体系,进一步运用模糊认知图模型(FCM)和人工神经网络(ANN)开展生态移民安置区生态风险识别.结果表明: 从利益相关者群体生态风险变量认知来看,其共同点是不同利益群体对垃圾污染风险变量提及数量最多,但整体上又存在显著差异,即管理者注重环境保护政策的制定和实施;居民则关注生活水平的提高,且直接关系到其环保意识和行为;经济活动者多追求经济利益;环境保护者专注于生态环境问题.不同利益相关者群体认知图论指数结果显示,管理者和环境保护者对安置区生态风险认知较为全面且清晰.从安置区4方利益相关者的整体风险认知结果来看,生态环境风险因子显著影响居民的人身安全及满意度;公共政策对安置区风险管理起关键作用;风险变量的中心度结果进一步表明,提高居民生活水平是防范生态风险的关键.从利益相关者群体生态风险感知与管理情景模拟结果来看,解决垃圾污染有助于生态环境整体改善,且关键是要完善和落实相关公共政策;建立健全社会保障制度,直接关系居民生活水平和环保行为;加强基础设施建设,影响景观生态格局、生物生境和多样性,同时可提高居民满意度和公众参与度.     

转基因作物在南非的应用及对我国的启示*

2019年是南非转基因作物商业化种植的第22年,3种主要转基因作物:棉花、玉米和大豆共种植了268万公顷,在全球所有转基因作物生产国中排名第八位,在非洲大陆排名第一位。这样一个具有超高转基因作物应用率的国家,有关其转基因商业化进程及现状鲜有系统介绍。综合1996~2019年的国际农业生物技术应用服务组织(International Service for the Acquisition of Agri-biotech Applications,ISAAA)的报告及其他数据资料,对南非转基因作物批准和种植情况、自主研发情况、安全管理制度、进出口情况及公众接受度做了概述,并以此为基础对我国转基因产业提出建议。     

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.     

Bringing Compassion to the Ethical Dilemma in Killing Kangaroos for Conservation

Ethical debate on the killing of kangaroos has polarised conservation and animal welfare science, yet at the heart of these scientific disciplines is the unifying aim of reducing harm to non-human animals. This aim provides the foundation for common ground, culminating in the development of compassionate conservation principles that seek to provide mechanisms for achieving both conservation and welfare goals. However, environmental decision-making is not devoid of human interests, and conservation strategies are commonly employed that suit entrenched positions and commercial gain, rather than valuing the needs of the non-human animals in need of protection. The case study on the wild kangaroo harvest presents just such a dilemma, whereby a conservation strategy is put forward that can only be rationalised by ignoring difficulties in the potential for realising conservation benefits and the considerable welfare cost to kangaroos. Rather than an open debate on the ethics of killing game over livestock, in this response I argue that efforts to bring transparency and objectivity to the public debate have to date been obfuscated by those seeking to maintain entrenched interests. Only by putting aside these interests will debate about the exploitation of wildlife result in humane, compassionate, and substantive conservation benefits.     

The Precautionary Principle,Science and Human Health Protection

As technology advances rapidly, so do applications with potential adverse implications on human health. The possible threats include risks that can be substantial, far-reaching and irreversible, and currently available methods of investigation, designed to deal with direct exposure-disease associations, are not always suitable. Growing interest is being paid to health effects that may be the consequence of distal, “upstream” determinants. Considering the complex chain of events that links such determinants with health can be extremely difficult, and exposes severe limitations in science. Thus, there is often a mismatch between what is known and what would be required to inform rational, evidence-based decision making, which is increasingly called for. It has become apparent how production and use of scientific evidence in decision making must be accompanied by precaution, especially in those circumstances, more and more common in recent times, where there is an uncertain possibility that serious health consequences might take place. Several cautionary approaches have been proposed, but the Precautionary Principle (PP) has been the object of especially intense debate in recent years. Developed in the field of environmental health, the PP has been clarified, and has been applied or called for in several instances in public health. Although a unique definition is not available, the principle has been characterised, and criteria for its application have been proposed. However, many questions remain open on general as well as specific issues. In this paper, we address some of the questions that are relevant for the PP to support rational decision making in environment and health and more in general to strengthen its contribution towards human health protection.     

Looks are deceiving: The portraits of Christopher Columbus

Since no portraits of the famed discoverer, Christopher Columbus, were made during his lifetime, an analysis of the images used to describe the physical attributes of the man and his place in history is an exercise in cultural relativism. Three time periods were studied: soon after his death when the public simply needed to know what the explorer looked like, hundreds of years after his explorations when commercial interests used Columbus as a symbol for their own further expansion into unknown territories, and during the present day when a majority of opinion about Columbus and his exploits is severely critical.     

Distributed structure-searchable toxicity (DSSTox) public database network: a proposal.

The ability to assess the potential genotoxicity, carcinogenicity, or other toxicity of pharmaceutical or industrial chemicals based on chemical structure information is a highly coveted and shared goal of varied academic, commercial, and government regulatory groups. These diverse interests often employ different approaches and have different criteria and use for toxicity assessments, but they share a need for unrestricted access to existing public toxicity data linked with chemical structure information. Currently, there exists no central repository of toxicity information, commercial or public, that adequately meets the data requirements for flexible analogue searching, Structure-Activity Relationship (SAR) model development, or building of chemical relational databases (CRD). The distributed structure-searchable toxicity (DSSTox) public database network is being proposed as a community-supported, web-based effort to address these shared needs of the SAR and toxicology communities. The DSSTox project has the following major elements: (1) to adopt and encourage the use of a common standard file format (structure data file (SDF)) for public toxicity databases that includes chemical structure, text and property information, and that can easily be imported into available CRD applications; (2) to implement a distributed source approach, managed by a DSSTox Central Website, that will enable decentralized, free public access to structure-toxicity data files, and that will effectively link knowledgeable toxicity data sources with potential users of these data from other disciplines (such as chemistry, modeling, and computer science); and (3) to engage public/commercial/academic/industry groups in contributing to and expanding this community-wide, public data sharing and distribution effort. The DSSTox project's overall aims are to effect the closer association of chemical structure information with existing toxicity data, and to promote and facilitate structure-based exploration of these data within a common chemistry-based framework that spans toxicological disciplines.     

Intellectual property protection for plant-related inventions in Europe

The economic and political issues that accompany the commercial growing of genetically modified crops, as well as the risk of transgene spread, are often top of the agenda for debate. But one important aspect is frequently overlooked--the intellectual property protection of plant-related inventions. What protection does European patent law afford to such inventions, how does it compare with the United States law and what are the consequences of the differences between them?