An assessment of the use of chimpanzees in hepatitis C research past, present and future: 1. Validity of the chimpanzee model

The USA is the only significant user of chimpanzees in biomedical research in the world, since many countries have banned or limited the practice due to substantial ethical, economic and scientific concerns. Advocates of chimpanzee use cite hepatitis C research as a major reason for its necessity and continuation, in spite of supporting evidence that is scant and often anecdotal. This paper examines the scientific and ethical issues surrounding chimpanzee hepatitis C research, and concludes that claims of the necessity of chimpanzees in historical and future hepatitis C research are exaggerated and unjustifiable, respectively. The chimpanzee model has several major scientific, ethical, economic and practical caveats. It has made a relatively negligible contribution to knowledge of, and tangible progress against, the hepatitis C virus compared to non-chimpanzee research, and must be considered scientifically redundant, given the array of alternative methods of inquiry now available. The continuation of chimpanzee use in hepatitis C research adversely affects scientific progress, as well as chimpanzees and humans in need of treatment. Unfounded claims of its necessity should not discourage changes in public policy regarding the use of chimpanzees in US laboratories.     

A view from the NIH bridge: perspectives of a program officer

This essay is written from my perspective as a program officer for research and training activities at the National Institute of General Medical Sciences (NIGMS) for almost 27 yr. It gives a bird's-eye view of the job of a program officer, which includes providing advice to applicants and grantees, making funding recommendations, overseeing grantees' progress, facilitating scientific opportunities in specific areas of program responsibility, and shaping NIGMS and National Institutes of Health (NIH) policy. I have highlighted the numerous rewards of serving as a program officer, as well as some of the difficulties. For those who may be considering a position as an NIH program officer now or in the future, I've also described the qualities and qualifications that are important for such a career choice. Finally, this essay addresses some of the challenges for the NIH and the research community in the years ahead as we simultaneously face exciting scientific opportunities and tighter budgets.     

The National Institutes of Health system for enhancing the science,safety, and ethics of recombinant DNA research

Oversight of recombinant DNA research by the National Institutes of Health (NIH) is predicated on ethical and scientific responsibilities that are akin, in many ways, to those that pertain to the oversight of animal research. The NIH system of oversight, which originated more than 25 years ago, is managed by the NIH Office of Biotechnology Activities (OBA), which uses various tools to fulfill its oversight responsibilities. These tools include the NIH Guidelines for Research Involving Recombinant DNA Molecules (NIH Guidelines) and the Recombinant DNA Advisory Committee. The OBA also undertakes special initiatives to promote the analysis and dissemination of information key to our understanding of recombinant DNA, and in particular, human gene transfer research. These initiatives include a new query-capable database, an analytical board of scientific and medical experts, and conferences and symposia on timely scientific, safety, and policy issues. Veterinary scientists can play an important role in the oversight of recombinant DNA research and in enhancing our understanding of the many safety and scientific dimensions of the field. These roles include developing appropriate animal models, reporting key safety data, enhancing institutional biosafety review, and promoting compliance with the NIH Guidelines.     

Two strikes: limited NIH R55 and R56 retooling funds and abolishment of the A2 grant mechanism

The U.S. National Institutes of Health (NIH) are facing significant budgetary challenges as a result of the current economic climate. The recent sunset of investigator-initiated R01-type research grants after one revised submission, coupled with the present lack of an NIH retooling funding mechanism for such grant applicants, creates a concerning risk that talented and well-trained investigators may be forced to give up their research careers. Existing NIH retooling mechanisms include the R55 Shannon Award, which was established in 1991 and was essentially replaced in 2005 by the R56 award. There is an urgent need to either significantly expand the R55/R56 mechanisms and definition of NIH grant bridging/retooling support for unfunded meritorious proposals or introduce a new mechanism that provides specific support to investigators with competitive but unfunded R01 revised grants. An expanded retooling funding mechanism deserves implementation during continuing assessment of whether allowance of only one revision of research proposals has achieved its initial intended goals.     

Immunology for the next generation

Immunologists need to establish a vibrant dialogue with young people. This is not only important for the continuation and progress of biomedical research, but it can also contribute to the fight against diseases such as HIV/AIDS and can help young people to make informed decisions about lifestyle, medical treatment and ethical issues. Good communication skills are crucial to any scientific career, and the lessons learned from talking with non-scientists can also be useful when writing scientific papers and grants. This article is a personal account of one scientist's experience of communicating biomedical science to young people.     

Biomedical research funding: when the game gets tough, winners start to play

Extramural funding provides major support for biomedical research in academia, and National Institutes of Health (NIH) grants often constitute direct evaluation criteria for promotions and tenure. Therefore, NIH budget trends influence long-term scientific strategies and career decisions, as well as the progress of science itself. Our analysis of the last 37 years of NIH awards, however, reveals that the success rate of grant applications submitted for funding is negatively related to the total yearly amount of (inflation-adjusted) NIH extramural expenditure. Instead, as might be expected, the ratio between available funding and the number of submission directly predicts the probability of winning support in any given year. We purport that the considerable success rate variability can be parsimoniously explained by a proportional but delayed reaction of the number of applications to budget fluctuations. As a counterintuitive consequence, grant proposals conceived during lean periods might stand the best chance of success.     

美国国立卫生研究院概况

美国国立卫生研究院(the National Institutes of Health,NIH)是美国主要的医学与行为学(medical and behavioral research)研究机构,拥有27个研究所及研究中心和1个院长办公室(office of the director,OD),任务是探索生命本质和行为学方面的基础知识,并充分运用这些知识延长人类寿命,以及预防、诊断和治疗各种疾病和残障。NIH不仅拥有自己的实验室从事医学研究,还通过各种资助方式和研究基金全力支持各大学、医学院校、医院等的非政府科学家及其他国内外研究机构的研究工作,并协助进行研究人员培训,促进医学信息交流。世界一流的科学家在NIH的支持下,自由探索科学问题,取得了辉煌的成就,极大地改善了人类的健康和生存状况。本文旨在介绍NIH的概况、基金管理模式、经费预算等,希望对我国的医学研究事业有所借鉴。     

A plan for the mouse genome project

The National Center for Human Genome Research and the Department of Energy convened a committee of geneticists and biologists who use the laboratory mouse in their research programs. Their responsibility was to identify goals and guidelines for completing the genetic and physical maps of the mouse genome. The motivation for convening this group was to make certain that existing and anticipated research projects together represent a comprehensive program for addressing the Five Year Goals of the Human Genome Project. Three meetings were held: the first addressed the contributions that the mouse can make to the Human Genome Project; the second meeting reviewed the status of the genetic map, gene mapping research, and genome informatics; and the final meeting evaluated the status of the physical map and physical mapping research. The committee then prepared a report that reviewed the status of the mouse genome project and made recommendations concerning areas of research emphasis. The resulting Request For Applications entitled Mapping the Mouse Genome with Emphasis on Technology Development (RFA: HG92-002) is an important mechanism for coordinating mouse genome research and accomplishing the goals of the mouse genome project. Progress towards complete genetic and physical maps has been impressive. The genetic map should be completed on schedule, and ongoing physical mapping projects are promising. Given rapid progress on these maps, the Working Group proposed expanding the focus of the mouse genome effort to begin planning comprehensive approaches for characterizing the function of the large number of genes that will soon be mapped and eventually sequenced. Partly as a consequence of the Working Group's efforts, discussions have begun among members of the scientific community and National Institutes of Health (NIH) staff to plan comprehensive, efficient, and innovative approaches for studying gene function. The Working Group prepared a report summarizing the status of mouse genome research and recommending areas where effort and funding should be placed. Our report was submitted to and accepted by the NIH and Department of Energy (DOE) and is published here in its entirety.Verne M. Champman, Chair, Neal G. Copeland, Franklin D. Costantini, William F. Dove, Joseph H. Nadeau, Roger H. Reeves, Janet Rossant, Oliver Smithies, and Richard P. Woychik.     

Correlates of Research Effort in Carnivores: Body Size,Range Size and Diet Matter

Given the budgetary restrictions on scientific research and the increasing need to better inform conservation actions, it is important to identify the patterns and causes of biases in research effort. We combine bibliometric information from a literature review of almost 16,500 peer-reviewed publications on a well-known group of 286 species, the Order Carnivora, with global datasets on species'' life history and ecological traits to explore patterns in research effort. Our study explores how species'' characteristics influenced the degree to which they were studied (measured as the number of publications). We identified a wide variation in intensity of research effort at both Family and Species levels, with some of the least studied being those which may need protection in future. Our findings hint at the complex role of human perspectives in setting research agendas. We found that better-studied species tended to be large-bodied and have a large geographic range whilst omnivory had a negative relationship with research effort. IUCN threat status did not exhibit a strong relationship with research effort which suggests that the conservation needs of individual species are not major drivers of research interest. This work is the first to use a combination of bibliometric analysis and biological data to quantify and interpret gaps in research knowledge across an entire Order. Our results could be combined with other resources, such as Biodiversity Action Plans, to prioritise and co-ordinate future research effort, whilst our methods can be applied across many scientific disciplines to describe knowledge gaps.     

Training strategies for research investigators and technicians

Training programs for research personnel are discussed as a key resource that must be part of an effective animal care and use program. Because of the legal responsibility to ensure that research staff are qualified to use animals, many institutions have justified the necessity for a training coordinator and/or trainers for their animal care and use programs. Effective training programs for research personnel must meet the needs of the client base (research scientists and staff) so that they are relevant, practical, and timely. To meet these objectives, it is useful to involve the scientific staff in the analysis of their learning needs. To meet a performance standard necessary for quality research, a large percentage of the institutional staff must participate in the training program. Often it is the principal investigators who set the tone for their staff members regarding the importance of receiving training. Garnering support from this client base will create a culture that encourages training and engenders a positive attitude about humane animal care and use. One effective approach is to incorporate nonanimal models as alternatives to live animals to teach humane handling techniques and methods, thereby contributing to refinement, reduction, and replacement (the 3Rs). Also discussed are the necessity of timely feedback from clients, documentation of personnel training for regulatory purposes, and the collection of training metrics, which assists in providing justification for the granting of additional fiscal support for the program. Finally, the compliance procedures and opportunities for essential refresher training are discussed and related to high performance standards, humane animal use, and quality research, all of which contribute to the 3Rs.     

Postapproval monitoring and the role of the compliance office

Postapproval monitoring (PAM) of research animal use is becoming increasingly common, and the compliance office plays a leading supportive role for the institutional animal care and use committee (IACUC) in implementing PAM at many institutions. Several other groups--higher administration, veterinary and husbandry staff, scientific staff, and occupational health and safety--are important participants in the process, and the compliance office should strive to work collegially with them as a team that facilitates research while meeting compliance requirements. Maintaining a cooperative and open attitude and developing an interest in the science will enhance the research staff's trust in both the compliance office and the PAM program. Resources required by the compliance office to oversee PAM include adequate physical facilities, funding, personnel, and time. Of these, appropriately trained quality assurance coordinators who have the requisite interpersonal and communication skills to interact constructively with researchers are vitally important. Education is key to minimizing the possibility of postapproval noncompliance, and the director of the compliance office, together with the quality assurance coordinators, should assume responsibility for teaching the IACUC, research staff, and higher administration about compliance requirements as well as correct practices and improved techniques. Postapproval noncompliance will occur despite even the best-run PAM program, and adequate documentation and communication will be necessary to address it. The compliance office, on behalf of the IACUC, should assume a primary role in facilitating the institutional response to noncompliance.     

Counting Highly Cited Papers for University Research Assessment: Conceptual and Technical Issues

A Kuhnian approach to research assessment requires us to consider that the important scientific breakthroughs that drive scientific progress are infrequent and that the progress of science does not depend on normal research. Consequently, indicators of research performance based on the total number of papers do not accurately measure scientific progress. Similarly, those universities with the best reputations in terms of scientific progress differ widely from other universities in terms of the scale of investments made in research and in the higher concentrations of outstanding scientists present, but less so in terms of the total number of papers or citations. This study argues that indicators for the 1% high-citation tail of the citation distribution reveal the contribution of universities to the progress of science and provide quantifiable justification for the large investments in research made by elite research universities. In this tail, which follows a power low, the number of the less frequent and highly cited important breakthroughs can be predicted from the frequencies of papers in the upper part of the tail. This study quantifies the false impression of excellence produced by multinational papers, and by other types of papers that do not contribute to the progress of science. Many of these papers are concentrated in and dominate lists of highly cited papers, especially in lower-ranked universities. The h-index obscures the differences between higher- and lower-ranked universities because the proportion of h-core papers in the 1% high-citation tail is not proportional to the value of the h-index.     

Italian natural history museums on the verge of collapse?

The Italian natural history museums are facing a critical situation, due to the progressive loss of scientific relevance, decreasing economic investments, and scarcity of personnel. This is extremely alarming, especially for ensuring the long-term preservation of the precious collections they host. Moreover, a commitment in fieldwork to increase scientific collections and concurrent taxonomic research are rarely considered priorities, while most of the activities are addressed to public events with political payoffs, such as exhibits, didactic meetings, expositions, and talks. This is possibly due to the absence of a national museum that would have better steered research activities and overall concepts for collection management. We here propose that Italian natural history museums collaborate to instate a “metamuseum”, by establishing a reciprocal interaction network aimed at sharing budgetary and technical resources, which would assure better coordination of common long-term goals and scientific activities.     

Global harmonization in the care and use of laboratory animals for the space life science research]

Space researches are supported with the international space agencies, NASA and NASDA. Animal experiments on the space life science must conform to the NIH policies and the NASA guide for the care and use of laboratory animals. The goal of the NIH policies is to promote the humane care of animals used biomedical and behavioral research, teaching, and testing. In each institute, the Institutional Animal Care and Use Committee (IACUC) plays an important role in conformity with NIH policies. The IACUC is charged with developing, recommending and monitoring NIH/NASA (ARC and KSC) policies, guides and rules relating to animal acquisition, care and use. In ARC and KSC, investigators will be responsible only for activities directly related to the conduct of their animal experiments. Even if researchers have protocols of the space science in Japan, the animal experiment should be carried out under the global harmonized conditions in accordance with NIH policies and NASA guides.     

Rice functional genomics research in China

Rice functional genomics is a scientific approach that seeks to identify and define the function of rice genes, and uncover when and how genes work together to produce phenotypic traits. Rapid progress in rice genome sequencing has facilitated research in rice functional genomics in China. The Ministry of Science and Technology of China has funded two major rice functional genomics research programmes for building up the infrastructures of the functional genomics study such as developing rice functional genomics tools and resources. The programmes were also aimed at cloning and functional analyses of a number of genes controlling important agronomic traits from rice. National and international collaborations on rice functional genomics study are accelerating rice gene discovery and application.     

基于HIS模型建立肝病知识库对军队医院的作用及意义

目的:通过整合302医院丰富的肝病病例、肝病专家诊疗经验和临床科研数据,建立肝病知识库,提高基础资源辅助临床诊疗和科研的能力。方法:对肝病智能知识模型进行分析,获取知识库中结构化知识,并以知识库模型的形式建立知识库,形成一套独立、可重复的智能化的辅助诊疗和科研信息系统,实现知识库辅助临床诊疗、知识科学研究,最大程度发挥知识库的意义,真正为临床服务。结果:建立的基于HIS的肝病知识库主要编配于医疗单位,适用于临床医护人员、临床科研人员以及所有从事医疗行业的工作人员。医护工作者可通过程序访问知识库,对知识库中的肝病知识进行检索、分析、推理,辅助临床医护工作者提高临床诊疗能力,提升临床科研水平。结论:建立的肝病知识库系统为用户提供横向及纵向医疗基础信息的检索、分析及推理方法。推理出的合适的知识模型,为肝病的临床诊疗和临床科研提供前沿、实用、高效的智能辅助信息支持。     

NIH initiative to balance sex of animals in preclinical studies: generative questions to guide policy,implementation, and metrics

In May of 2014, the NIH Director together with the Director of the Office of Research on Women’s Health announced plans to take a multi-dimensional approach to address the over reliance on male cells and animals in preclinical research. The NIH is engaging the scientific community in the development of policies to improve the sex balance in research. The present, past, and future presidents of the Organization for the Study of Sex Differences, in order to encourage thoughtful discussion among scientists, pose a series of questions to generate ideas in three areas: 1. research strategies, 2. educational strategies, and 3. strategies to monitor effectiveness of policies to improve the sex balance in research. By promoting discussion within the scientific community, a consensus will evolve that will move science forward in a productive and effective manner.     

Framework to improve the application of theory in ecology and conservation

Ecological theory often fails applied ecologists in three ways: (1) Theory has little predictive value but is nevertheless applied in conservation with a risk of perverse outcomes, (2) individual theories have limited heuristic value for planning and framing research because they are narrowly focused, and (3) theory can lead to poor communication among scientists and hinder scientific progress through inconsistent use of terms and widespread redundancy. New approaches are therefore needed that improve the distillation, communication, and application of ecological theory. We advocate three approaches to resolve these problems: (1) improve prediction by reviewing theory across case studies to develop contingent theory where possible, (2) plan new research using a checklist of phenomena to avoid the narrow heuristic value of individual theories, and (3) improve communication among scientists by rationalizing theory associated with particular phenomena to purge redundancy and by developing definitions for key terms. We explored the extent to which these problems and solutions have been featured in two case studies of long-term ecological research programs in forests and plantations of southeastern Australia. We found that our main contentions were supported regarding the prediction, planning, and communication limitations of ecological theory. We illustrate how inappropriate application of theory can be overcome or avoided by investment in boundary-spanning actions. The case studies also demonstrate how some of our proposed solutions could work, particularly the use of theory in secondary case studies after developing primary case studies without theory. When properly coordinated and implemented through a widely agreed upon and broadly respected international collaboration, the framework that we present will help to speed the progress of ecological research and lead to better conservation decisions.     

Decoding the research exemption

While debate continues as to whether genetic sequences, which many argue represent natural phenomena rather than inventions, should be subject to standard patent protections, issuance of patents that claim DNA sequences remains common practice. In an attempt to insulate researchers from patent claims that could hinder scientific progress, many countries have provided general exemptions for scientific research. However, there is no international consensus about the extent of required protections, and even existing exemptions vary widely in clarity and are limited in practical application. We believe that gene patents raise several unique issues that are inadequately handled by the current research exemptions.     

Role of nuclear analytical probe techniques in biological trace-element research

Many biomedical experiments require the qualitative and quantitative localization of trace elements with high sensitivity and good spatial resolution. The feasibility of measuring the chemical form of the elements, the time course of trace element metabolism, and conducting experiments in living biological systems are also important requirements for biological trace element research. Nuclear analytical techniques that employ ion or photon beams have grown in importance in the past decade and have led to several new experimental approaches. Some of the important features of these methods are reviewed here along with their role in trace element research. Examples of their use are given to illustrate potential for new research directions. It is emphasized that the effective application of these methods necessitates a closely integrated multidisciplinary scientific team.