Germline gene editing and the precautionary principle

The precautionary principle aims to influence decision-making in contexts where some activity poses uncertain but potentially grave threats. This perfectly describes the controversy surrounding germline gene editing. This article considers whether the precautionary principle should influence how we weigh the risks and benefits of human germline interventions, focusing especially on the possible threats to the health of future generations. We distinguish between several existing forms of the precautionary principle, assess their plausibility and consider their implications for the ethics of germline modification. We also offer a novel form of the precautionary principle: the sufficientarian precautionary principle. Some plausible versions of the precautionary principle recommend placing somewhat greater weight on avoiding threats to future generations than on achieving short-term benefits. However, no plausible versions of the precautionary principle entail that we should outright reject the use germline gene editing in human reproduction and some, such as the sufficientarian version, might endorse its use.     

Avoiding the Trust Deficit: Public Engagement, Values, the Precautionary Principle and the Future of Nanotechnology

Debates about the regulatory requirements surrounding the introduction of nanotechnology products have, at least in Australia, remained largely within disciplinary boundaries and industry and academic circles. This paper argues for a more interdisciplinary and inclusive upstream debate about the introduction of ethical, regulatory and legal frameworks that may avoid the loss of public trust that has characterised the introduction of many new technologies in the past. Insights from risk-perception theory and research are used to introduce the notion of risk as narrative as a framework for action. This paper suggests three main strategies for moving forward; drawing insights from the “trust gap” experiences of other new technologies; the application of the active form of the precautionary principle; and, the creation of nano-futures that meet both community and industry values through effective public engagement.     

Xenotransplantation, endogenous pig retroviruses and the precautionary principle

Xenotransplantation poses challenges to scientists, ethicists and clinicians. Recent studies of the role of endogenous retroviruses suggest that these agents could threaten the safety of porcine xenotransplantation both for the recipient of a transplant, and possibly for people who have contact with that patient. Although the risk of such complications is low, the history of recent infectious diseases suggests that the precautionary principle should be invoked.     

美国与欧盟的转基因食品安全性政策演变比对

随着转基因食品的研究与发展,人们对待转基因食品的态度表现为主要以美国和欧盟为主的两种代表性政策.美国采取遵循可靠科学原则,坚决反对预防原则,即对转基因食品采取积极支持,自愿标识的宽松政策;欧盟采取谨慎预防原则,必须标识和可追溯.从管理原则出发,结合相应采取的监管措施和相关条例,对两国从开始颁布转基因食品政策到当下态势的发展,并结合最新出台的政策进行跟踪分析,比对美国及欧盟对这些指令和条例的执行情况.     

Selected applications of reduced uncertainty factors in noncancer risk assessment

Guidelines have been developed within the Environmental Protection Agency (EPA) for applying uncertainty factors to noncancer risk assessments. In many recent cases, reduced values for uncertainty factors of less than 10 have been used. The specific circumstances that justify reduced uncertainty are: partial definition of the sensitive subpopulation among humans, partial database limitations, use of a minimal LOAEL, risk assessment for an essential nutrient, and risk assessments based upon studies in nonhuman primates. Details of the rationale for each of these circumstances are provided.     

Incorporating Science,Technology, Fairness,and Accountability in Environmental,Health, and Safety Decisions

The Precautionary Principle is in sharp political focus today because (1) the nature of scientific uncertainty is changing and (2) there is increasing pressure to base governmental action on more “rational” schemes, such as cost-benefit analysis and quantitative risk assessment, the former being an embodiment of ‘rational choice theory’ promoted by the Chicago school of law and economics. The Precautionary Principle has been criticized as being both too vague and too arbitrary to form a basis for rational decision making. The assumption underlying this criticism is that any scheme not based on cost-benefit analysis and risk assessment is both irrational and without secure foundation in either science or economics. This paper contests that view and makes explicit the rational tenets of the Precautionary Principle within an analytical framework as rigorous as uncertainties permit, and one that mirrors democratic values embodied in regulatory, compensatory, and common law. Unlike other formulations that reject risk assessment, this paper argues that risk assessment can be used within the formalism of tradeoff analysis—a more appropriate alternative to traditional cost-benefit analysis and one that satisfies the need for well-grounded public policy decision making. This paper will argue that the precautionary approach is the most appropriate basis for policy, even when large uncertainties do not exist, especially where the fairness of the distributions of costs and benefits of hazardous activities and products are a concern. Furthermore, it will offer an approach to making decisions within an analytic framework, based on equity and justice, to replace the economic paradigm of utilitarian cost-benefit analysis.     

A toxicological basis to derive generic interspecies uncertainty factors for application in human and ecological risk assessment

A new method is proposed to derive the size of the interspecies uncertainty factor (UF) that is toxicologically and statistically based. The method is based on the biological/evolutionary assumption that similarity in susceptibility to toxic substances is a function of phylogenetic relatedness. This assumption is assessed via a large and highly structured aquatic database with over 500 agents tested in specific binary toxicity comparison (i.e., when two species have been tested with the same chemical under identical conditions) for dozens of species of wide phylogenetic relatedness. The methodology takes into account the generic need to estimate a response in any species (not just human) and the need to predict responses for new chemical agents. The method involves quantifying interspecies variation in susceptibility to numerous toxic substances via the use of binary interspecies comparisons that are converted to a 95% UF. This interspecies UF represents an estimate of the upper 95% of the population of 95% prediction intervals (PI) for binary interspecies comparisons within four categories of phylogenetic relatedness (species‐within‐genus, genera‐within‐family, families‐within‐order, orders‐within‐class). The 95% interspecies UFs range from a low of 10 for species‐within‐genus up to 65 for orders‐within‐class. Most mammalian toxicology studies involving mice, rats, cats, dogs, gerbils, and rabbits are orders‐within‐class categories for human risk assessment and would be provided a 65‐fold UF. Larger or smaller interspecies UF values could be selected based on the level of protection desired. The procedures described have application to both human and ecological risk assessment.     

Calling the tunes on transgenic crops: the case for regulatory harmony

Genetically modified (GM) crops are now grown commercially in 23 countries, with another 29 granting approval for import and release into the environment. Despite the socio-economic and environmental benefits of the technology, further development is being hampered by differences in national regulatory frameworks relating to research, biosafety, and to the trade and use of GM crops. The biosafety regulations in different countries are based on five main international instruments that influence the development of national biosafety systems in terms of field trial permit requirements, risk assessment criteria, labeling, traceability, transparency, public awareness, post-monitoring and import regulations. The global harmonization of data collection, testing procedures and information exchange would help to remove artificial trade barriers, expedite the adoption of GM crops, foster technology transfer and protect developing countries from exploitation, instilling confidence and bringing the benefits of GM products to the consumer.     

Impact of abundance data errors on the uncertainty of an ecological water quality assessment index

Increased awareness about the uncertainty of ecological water quality (EWQ) assessment tools in river management has led to the identification of the underlying uncertainty sources and the quantification of their effect on assessment. More specifically, with respect to macroinvertebrate-based EWQ assessment, use of erroneous abundance data has been identified as a (possible) source of uncertainty. In this paper, the effect of erroneous abundance data on the uncertainty of an EWQ assessment index was investigated. A model simulation based method, the virtual ecologist approach, was used to estimate the impact of abundance data errors on the uncertainty of the Multimetric Macroinvertebrate Index Flanders (MMIF). The results of this study show that the effects of relative small errors on the MMIF and assessment are limited. Additionally, it is observed that uncertainties due to abundance errors increase with decreasing EWQ (i.e. lower MMIF). This is important, since decision-makers typically formulate management actions for rivers with a low EWQ. In short, the innovative virtual ecologist approach proved to be very successful to research the index uncertainty and present a unique insight in the functioning of the assessment index.     

乳腺癌术后医院感染患者病原菌分布和危险因素及血清炎症因子水平分析

目的分析乳腺癌术后医院感染患者病原菌分布、危险因素及血清炎症因子水平,并探讨其临床意义。方法收集2016年3月至2018年3月我院诊治的80例乳腺癌术后医院感染患者为观察组。同期选取80例乳腺癌术后未发生感染者为对照组。利用全自动微生物分析仪对感染患者进行病原菌分布检测。对乳腺癌术后医院感染的危险因素进行单因素回归分析,同时检测并比较两组患者血清中白细胞介素-10(IL-10)、干扰素-γ(IFN-γ)及肿瘤坏死因子-α(TNF-α)的水平。结果80例乳腺癌术后医院感染患者共检出病原微生物97株。其中革兰阴性菌55株,以大肠埃希菌及铜绿假单胞菌为主;革兰阳性菌39株,以金黄色葡萄球菌为主(16株);真菌3株。观察组患者血清中IL-10、INF-γ及TNF-α水平均显著高于对照组(均P<0.05)。患者合并疾病情况、引流天数、住院天数及辅助化疗均与乳腺癌术后发生医院感染有密切联系(均P<0.05)。结论乳腺癌术后医院感染病原菌分布较广,以革兰阴性菌为主。患者合并疾病情况、引流天数、住院天数及辅助化疗均为医院感染的危险因素。血清中炎症因子水平可作为乳腺癌术后医院感染的诊断标志物。     

Studies on the use of uncertainty factors in deriving RfDs

Risk assessment of exposure to chemicals having a toxic end point routinely uses the reference dose (RfD) approach based on uncertainty factors of 10. RfD model can be used with widely different databases. However, the quality of individual risk assessment is unequal among chemicals, often resulting in either an over‐ or underestimation of adverse health risk. The purpose of this investigation was to evaluate whether the magnitude of the 10X uncertainty factors has scientific merit against data from recent human and animal experimental studies. Although we assessed the use of uncertainty factors for representative chemicals from various classes of compounds, such as volatile organics, alcohols, gasoline components, and pesticides, we are presenting our findings for 24 chemicals.

A compilation and comparison of ratios between LOAEL/NOAEL (Lowest Observed Adverse Effect Level/No Observed Adverse Effect Level), and subchronic/chronic values were made. Although a 10X uncertainty factor is most commonly used in the risk assessment processes, an examination of the datasets which have been used to calculate RfDs suggests different values which are scientifically justifiable.     

广泛接种乙肝疫苗后不同年龄人群急性乙型肝炎危险因素的对应分析

目的研究广泛开展新生儿乙肝疫苗接种后,不同年龄人群中的乙型肝炎危险因素与年龄的对应关系,以制定针对性的乙型肝炎防治措施。方法回顾性分析40例乙型肝炎病毒感染者的感染危险因素,数据分析采用对应的分析方法。结果40例乙型肝炎病毒感染者中,低年龄组、母亲怀孕及分娩时感染乙型肝炎病毒有一定的联系。结论乙型肝炎的传播途径复杂。在低年龄组人群中,母婴传播是主要的传播途径。在低年龄组人群中开展乙肝疫苗接种是预防和控制乙型肝炎的重要措施。     

深圳地区50～70岁中老年人群10年缺血性心血管病发病风险预测

目的:了解深圳地区50~70岁中老年人群ICVD危险因素的暴露情况及对未来10年的ICVD患病风险进行评估,为深圳地区ICVD的防治提供依据。方法:选取2013年10月至2014年1月在香港大学深圳医院体检中心进行健康体检的1092名50~70岁中老年人群作为研究对象,对其体检资料和检查结果进行分析,应用"国人ICVD10年发病危险度评估方法 "模型,对研究对象ICVD10年发病危险度进行评估。结果:在1092名研究对象中,高血压、超重(或)肥胖、高脂血症、吸烟、糖尿病的暴露率分别为37.64%、51.19%、56.87%、29.58%、23.46%;男性的超重/肥胖、吸烟和糖尿病的暴露率高于女性,而女性高脂血症的暴露率高于男性,差异有统计学意义(P0.05);ICVD10年发病绝对危险度极低危、低危、中危、高危及极高危的检出率分别为65.02%、20.14%、10.26%、4.12%、0.46%;所有年龄组平均危险度水平均高于中国人群评估方法参考标准。结论:深圳地区50~70岁中老年人群ICVD发病危险因素暴露水平较高,ICVD10年发病风险较大,应积极进行健康教育及加强对ICVD危险因素的有效干预。     

Herbivore and pathogen damage on grassland and woodland plants: a test of the herbivore uncertainty principle

Researchers can alter the behaviour and ecology of their study organisms by conducting such seemingly benign activities as non-destructive measurements and observations. In plant communities, researcher visitation and measurement of plants may increase herbivore damage in some plant species while decreasing it in others. Simply measuring plants could change their competitive ability by altering the amount of herbivore damage that they suffer. Currently, however, there is only limited empirical evidence to support this `herbivore uncertainty principle' (HUP). We tested the HUP by quantifying the amount of herbivore and pathogen damage in 13 plant species (> 1400 individuals) at four different visitation intensities at Cedar Creek Natural History Area, Minnesota, USA. Altogether, we found very little evidence to support the HUP at any intensity of visitation. Researcher visitation did not alter overall plant herbivore damage or survival and we did not detect a significant visitation effect in any of the 13 species. Pathogen damage also did not significantly vary among visitation treatments, although there was some evidence that high visitation caused slightly higher pathogen damage. Based on our results, we question whether this phenomenon should be considered a `principle' of plant ecology.     

婴儿早期不同程度过敏风险高危因素大样本调查

目的通过大样本调查1～3月龄婴儿过敏风险,探讨影响婴儿过敏风险的高危因素。方法随机抽取我院2 188名健康查体的1～3月龄婴儿进行过敏风险程度评估,并对影响婴儿过敏风险程度的部分因素以及婴儿湿疹患病情况进行分析。结果本研究共发放问卷2 188份,全部回收,共剔除无效问卷101份,获得有效问卷2 087份,问卷有效率达95.38%。本研究中婴儿湿疹发病率为49.11%(1 025/2 087),且不同过敏风险婴儿湿疹的发生率不同(均P0.05)。生产方式、喂养方式、父母过敏性疾病史、孕期服用叶酸和孕期烟草烟雾暴露这5个因素与过敏风险关系显著(均P0.05)。性别、胎次、母亲学历、孕周、婴儿洗澡频率、房间通风频率、出生季节、1～3月龄母乳期回避海鲜间差异无统计学意义(均P0.05)。Logistic回归分析显示父母有过敏性疾病史、剖宫产、配方奶和部分人乳喂养、孕期服用叶酸、孕期烟草烟雾暴露为婴儿过敏性疾病发生的危险因素,OR值均1。结论婴儿期是过敏的易感时期,需要通过多种途径对婴儿进行过敏预防,早期过敏风险评估对降低婴儿过敏发生率具有重大意义。     

Synapse elimination,the size principle,and Hebbian synapses

Synapse elimination at the vertebrate neuromuscular junction reduces a polyinnervated population of muscle fibers to a monoinnervated state. The function of this developmental phenomenon (if any) is unproven. A theoretical analysis of Hebbian (correlation) rules connecting presynaptic and postsynaptic activity and synaptic strength at the neuromuscular junction is presented. The following points are demonstrated: (1) Correlational competition leads to the reduction of polyinnervation to a stable monoinnervated state; (2) the competition gives rise to the size principle over a wide range of the plausible parameter space; (3) over a significant subrange, the competition selectively eliminates topographically incorrect synapses; and (4) in cases in which topographic projection errors overwhelm the system, both error correction and the development of the size principle are disrupted. Correlational competition may explain contradictory experimental results concerning the effects of stimulating or silencing subpopulations of motor neurons. It may also explain an otherwise puzzling instance of a breakdown in the size principle seen in humans undergoing neural regeneration. Taken together, these findings suggest a novel hypothesis for the function of synapse elimination at the neuromuscular junction: the establishment of the size principle. © 1995 John Wiley & Sons, Inc.     

The economics of escape behaviour in the pea aphid,Acyrthosiphon pisum

Summary Pea aphids have several alternative responses to the detection of alarm pheromone produced by conspecifics. One of these, dropping from the feeding site to the ground, is potentially costly owing to the risk of desiccation-induced mortality on the ground before another host plant can be reached. Both dropping and walking from the feeding site incur a cost due to lost feeding opportunity. The aphids' decision as to which anti-predator tactic to use should be sensitive to the costs of their behaviour. Consequently, aphids should be less likely to drop when the risk of desiccation is higher, and less likely to drop or walk when the lost opportunity cost is higher. We tested these predictions by manipulating climatic severity (temperature and humidity) and host quality, respectively. As predicted, aphids are less likely to drop or walk in response to pheromone when feeding on high quality than on low quality hosts, and less likely to drop when the environment is hot and dry than when it is more benign. The latter is true whether the aphids are feeding on real or simulated leaves. Since all aphids were of the same clone, these results show that individual aphid genotypes possess the ability to adaptively modify their escape behaviour with changes in prevailing conditions. A number of other behavioural observations in the aphid literature may be interpreted in an economic or cost-benefit framework. The approach holds considerable promise for understanding many aspects of the anti-predator behaviour of aphids and other animals.