Managing biosecurity threats in China

Compared to the extensive literature on bioterrorism and biosecurity in the United States, less analysis has been conducted on similar challenges in China. This article seeks to fill this void by providing an integrated and updated assessment of 3 major biosecurity threats China faces: biowarfare, bioterrorism, and biocrimes. An analysis of China's biosecurity threats and biodefense building suggest varying levels of risk associated with each threat type. First, a direct bioweapons attack on China is highly unlikely, although the threat of biowarfare cannot be simply written off. Second, potential perpetrators of bioterrorism have capabilities at their disposal for carrying out such attacks. While terrorist organizations in China do not have a strong interest in bioterrorism, the limited state capability to counter such a threat may increase the risk in the future. Third, unlike the threats of biowarfare and bioterrorism, potential perpetrators of biocrimes have both incentives and capabilities, and biocrimes can produce reactions far out of proportion to the actual number of casualties. Despite the distinct biosecurity challenges it faces, China has yet to articulate a differentiated and coherent strategy to effectively tackle the challenges. Assessing different types of biosecurity threats in terms of degrees of risk not only provides greater analytical clarity but also has important implications for the strategies required to manage the risks.     

Casting a wider net for countermeasure R&D funding decisions

Among potential bioweapons attacks, endemic infectious diseases (that is, those naturally occurring diseases that afflict us every year), and a potential influenza pandemic, how should we apportion funding and resources for basic research and countermeasure development? To address this question, I argue for a "combined risk assessment" that considers bioweapons attacks with natural pandemics and endemic infectious disease. At present, risk assessments for bioweapons attacks are carried out separately from the assessments long carried out for endemic infectious diseases to make public health and medical care decisions. One result of this separation is that funding decisions may be unduly influenced by an overblown fear of a big bioweapons attack and by political whim. The result of the simplified combined risk assessment presented here argues for more funding and resources for endemic infectious disease and for placing biodefense against anthrax and other bioweapons in a place lower in the risk hierarchy. Since the assessment here considers only fatalities to make the point that our priorities are skewed, the conclusions are only a "first word" on the subject, far from the last. Furthermore, the impact of other issues on priorities, such as national and international policy, is not considered. It is a call for a debate on the public stage of the policy and other rationale and the quantitative risk assessment arguments that now place bioweapons attacks at the top of our risk ranking.     

The dual-use dilemma for the life sciences: perspectives, conundrums, and global solutions

The term "dual-use" traditionally has been used to describe technologies that could have both civilian and military usage, but this term has at least three different dimensions that pose a dilemma for modern biology and its possible misuse for hostile purposes: (1) ostensibly civilian facilities that are in fact intended for military or terrorist bioweapons development and production; (2) equipment and agents that could be misappropriated and misused for biological weapons development and production; and (3) the generation and dissemination of scientific knowledge that could be misapplied for biological weapons development and production. These three different aspects of the "dual-use dilemma" are frequently confused--each demands a distinct approach within a "web of prevention" in order to reduce the future risk of bioterrorism and biowarfare. This article discusses the nature of the different perspectives and divergent approaches as a contribution to finding a scientifically acceptable global solution to the problem posed by the dual-use dilemma. We propose that: (1) facilities that are intended for bioweapons development and production should be primarily prevented by a strengthened Biological and Toxin Weapons Convention (BTWC) effectively implemented in all nation states, one that includes provisions for adequate transparency to improve confidence and a mechanism for thorough inspections when there is sufficient cause, and enhanced law enforcement activities involving international cooperation and sharing of critical intelligence information; (2) potentially dual-use equipment and agents should be available to legitimate users for peaceful purposes, but strengthened national biosafety and physical and personnel biosecurity controls in all nations together with effective export controls should be implemented to limit the potential for the misappropriation of such equipment and materials; and (3) information should be openly accessible by the global scientific community, but a culture of responsible conduct involving the breadth of the international life sciences communities should be adopted to protect the ongoing revolution in the life sciences from being hijacked for hostile misuse of the knowledge generated and communicated by life scientists.     

BIRS – Bioterrorism Information Retrieval System

Bioterrorism is the intended use of pathogenic strains of microbes to widen terror in a population. There is a definite need to promote research for development of vaccines, therapeutics and diagnostic methods as a part of preparedness to any bioterror attack in the future. BIRS is an open-access database of collective information on the organisms related to bioterrorism. The architecture of database utilizes the current open-source technology viz PHP ver 5.3.19, MySQL and IIS server under windows platform for database designing. Database stores information on literature, generic- information and unique pathways of about 10 microorganisms involved in bioterrorism. This may serve as a collective repository to accelerate the drug discovery and vaccines designing process against such bioterrorist agents (microbes). The available data has been validated from various online resources and literature mining in order to provide the user with a comprehensive information system.

Availability

The database is freely available at http://www.bioterrorism.biowaves.org     

Striking against bioterrorism with advanced proteomics and reference methods

The intentional use by terrorists of biological toxins as weapons has been of great concern for many years. Among the numerous toxins produced by plants, animals, algae, fungi, and bacteria, ricin is one of the most scrutinized by the media because it has already been used in biocrimes and acts of bioterrorism. Improving the analytical toolbox of national authorities to monitor these potential bioweapons all at once is of the utmost interest. MS/MS allows their absolute quantitation and exhibits advantageous sensitivity, discriminative power, multiplexing possibilities, and speed. In this issue of Proteomics, Gilquin et al. (Proteomics 2017, 17, 1600357) present a robust multiplex assay to quantify a set of eight toxins in the presence of a complex food matrix. This MS/MS reference method is based on scheduled SRM and high‐quality standards consisting of isotopically labeled versions of these toxins. Their results demonstrate robust reliability based on rather loose scheduling of SRM transitions and good sensitivity for the eight toxins, lower than their oral median lethal doses. In the face of an increased threat from terrorism, relevant reference assays based on advanced proteomics and high‐quality companion toxin standards are reliable and firm answers.     

重要生物恐怖病原及其医学防护对策

生物恐怖问题由来已久,但直到美国“9.11”事件后的炭疽芽孢袭击才引起人们广泛关注。生物恐怖已成为21世纪全人类的威胁,防范生物恐怖病原袭击已成为各国政府的当务之急。本文主要介绍了对生物恐怖的定义、生物恐怖病原种类和致病特征,以及医学防护对策。     

Antibodies for biodefense

Potential bioweapons are biological agents (bacteria, viruses and toxins) at risk of intentional dissemination. Biodefense, defined as development of therapeutics and vaccines against these agents, has seen an increase, particularly in the US, following the 2001 anthrax attack. This review focuses on recombinant antibodies and polyclonal antibodies for biodefense that have been accepted for clinical use. These antibodies aim to protect against primary potential bioweapons or category A agents as defined by the Centers for Disease Control and Prevention (Bacillus anthracis, Yersinia pestis, Francisella tularensis, botulinum neurotoxins, smallpox virus and certain others causing viral hemorrhagic fevers) and certain category B agents. Potential for prophylactic use is presented, as well as frequent use of oligoclonal antibodies or synergistic effect with other molecules. Capacities and limitations of antibodies for use in biodefense are discussed, and are generally applicable to the field of infectious diseases.Key words: antibody, anthrax, plague, smallpox, botulism, tularemia, brucellosis, hemorrhagic, ricin, SEB     

Responsibility in the life sciences: assessing the role of professional codes

In response to threats from bioweapons, questions are being asked today in some countries about the implications and appropriateness of biological research. Many organizations and governments have suggested that bioscientists adopt what is generally referred to as a "code of conduct" to reduce the security concerns associated with their work. This article examines the potential contribution of such codes. By drawing on past lessons in other areas of professional life, it suggests some key questions, issues, and dilemmas for future consideration. As argued, attempts to establish codes must address demanding questions about their aims and audience--questions whose answers depend on potentially contentious issues regarding arms control, science, ethics, and politics.     

The HIPAA privacy rule and bioterrorism planning, prevention, and response

Effective bioterrorism planning, prevention, and response require information sharing between various entities, ranging from public health authorities and health-care workers to national security and law enforcement officials. While the source of much information exchanged may be nonidentifiable, many entities legitimately need access to personally identifiable health information (or "protected health information" [PHI]) in planning for and responding to a bioterrorism event. The HIPAA Privacy Rule allows for essential exchanges of health data during a public health emergency while protecting against unnecessary disclosures of PHI. In the event of a bioterrorist attack, the Privacy Rule allows covered entities to disclose PHI without individual authorization in the following instances: (1) for treatment by health-care providers, (2) to avert a serious threat to health or safety, (3) to public health authorities for public health purposes, (4) to protect national security, (5) to law enforcement under certain conditions, and (6) for judicial or administrative proceedings. Despite these favorable disclosure provisions, some privacy challenges remain. The flow of PHI may be slowed by misunderstandings of the Privacy Rule's accounting requirement. In addition, in a bioterrorism scenario, nontraditional entities may find themselves acting as health-care providers, triggering Privacy Rule provisions. Finally, the potential for de facto disclosures of individuals' disease or exposure status increases where conspicuous treatment methods, isolation, or quarantine are implemented without additional measures to protect privacy. Understanding the Privacy Rule's impact on bioterrorism planning and response ensures that various entities can conduct their activities with needed information while still protecting individual privacy.     

Leveraging bioterrorism preparedness for non-bioterrorism events: a public health example

When a local health department in Virginia learned that a deceased hospital-based nurse had worked for several months with undiagnosed and untreated active tuberculosis, it mounted an extraordinary effort to find, screen, test, and potentially treat numerous contacts. In responding to this challenge, it adapted plans, concepts, and equipment that had been recently developed or acquired for responding to acts of bioterrorism. The improved coordination and integration with community partners and participating agencies, fostered through bioterrorism preparedness planning, were keys to success. Using procedures developed and exercised to distribute prophylactic medication in the Strategic National Stockpile, the health department shifted philosophically from a program-specific response to a more integrated approach. Implementation of this mass tuberculosis-screening program was based on the principles of the Incident Command System (ICS). Owing to the efficiency of the operation, more than 2,500 people were quickly screened, and the rate of return for skin test readings was 91.6%, ranking it extremely high compared to the benchmarks. Overall, 5.9% of those tested were found to be infected with tuberculosis, and no cases of active tuberculosis were identified. This outcome demonstrated public health's improved ability to react, as a result of bioterrorism preparedness activities, to "traditional" public health mass events and non-bioterrorism emergencies.     

Missouri nurses' bioterrorism preparedness

Nurses are the largest group of healthcare providers and will be at the forefront during a response to a bioterrorism attack in the U.S. However, nurses' bioterrorism risk perceptions and their participation in bioterrorism preparedness activities, such as bioterrorism-related exercises or drills, have not been evaluated. We mailed a survey to all members of the Missouri Nurses Association in July 2006, consisting of 1,528 registered nurses. The instrument measured risk perception, perceived susceptibility, perceived seriousness, bioterrorism education received, participation in exercises/drills, and personal response plan thoroughness. The response rate was 31% (474/1,528). Most respondents believe that a bioterrorism attack will occur in the U.S. (82.3%; n = 390), but few (21.3%; n = 101) believe that one will occur in their community. The majority of nurses reported that they believe that a bioterrorism attack would have serious consequences (96.1%, n = 448), including having a serious impact on U.S. citizens' safety (90.7%, n = 446) and on their own safety (84.3%, n = 379). Most (60%, n = 284) reported that they had not received any bioterrorism-related education nor participated in any drills/exercises (82.7%, n = 392). Of those who had received education, most had participated in 3 or fewer programs and in only 1 drill. Few nurses (3.6%, n = 15) reported having all aspects of a personal bioterrorism response plan; approximately 20% (19.4%, n = 81) did not have any components of a plan. Most of the registered nurses in Missouri who were surveyed are not receiving bioterrorism education, participating in bioterrorism exercises, or developing thorough personal response plans. Nurses need to be aware of and encouraged to participate in the many education and training opportunities on bioterrorism and infectious disease disasters.     

Bioterrorism pressure on research agendas.

Governments and funding agencies are rapidly rethinking their funding for research on infectious agents that could be used as bioweapons following the anthrax outbreaks in the US. Laura Bonetta reports.     

Antibodies for biodefense

Potential bioweapons are biological agents (bacteria, viruses, and toxins) at risk of intentional dissemination. Biodefense, defined as development of therapeutics and vaccines against these agents, has seen an increase, particularly in the US following the 2001 anthrax attack. This review focuses on recombinant antibodies and polyclonal antibodies for biodefense that have been accepted for clinical use. These antibodies aim to protect against primary potential bioweapons, or category A agents as defined by the Centers for Disease Control and Prevention (Bacillus anthracis, Yersinia pestis, Francisella tularensis, botulinum neurotoxins, smallpox virus, and certain others causing viral hemorrhagic fevers) and certain category B agents. Potential for prophylactic use is presented, as well as frequent use of oligoclonal antibodies or synergistic effect with other molecules. Capacities and limitations of antibodies for use in biodefense are discussed, and are generally applicable to the field of infectious diseases.     

Strengthening bioterrorism prevention: global biological materials management

The anthrax attacks of 2001 demonstrated that bioterrorism poses a significant threat to U.S. national security. This threat is increasing as a result of the rapid expansion in scale and technical capabilities of the global biotechnology industry, which is broadening the availability of materials, technologies, and expertise needed to produce a biological weapon and is lowering the barriers to biological weapons terrorism and proliferation. At the same time, there has been a rise of sophisticated yet loosely networked transnational terrorist groups that have shown an interest in bioterrorism. The United States must confront this convergence. Although the U.S. government pursues many different biodefense programs to bolster its ability to detect and respond to a bioterrorist attack, these efforts must be augmented with preventive measures to meet today's international challenges. U.S. Homeland Security Presidential Directive 10 of April 2004 defines "Prevention and Protection" as one of the four essential pillars of the U.S. response to the bioterrorist threat. However, while bioscience and policy experts have proposed a variety of preventive initiatives, the creation of such programs has been slow and limited. Global biological materials management, which would focus on identifying and protecting those biological materials at the greatest risk of being used maliciously, is one potential solution. Such an approach would augment current U.S. biodefense efforts, provide the international community an effective means of mitigating the global threat of bioterrorism, and strengthen the international community's battle against emerging infectious disease.     

Structure- and substrate-based inhibitor design for Clostridium botulinum neurotoxin serotype A

The seven antigenically distinct serotypes of Clostridium botulinum neurotoxins cleave specific soluble N-ethylmaleimide-sensitive factor attachment protein receptor complex proteins and block the release of neurotransmitters that cause flaccid paralysis and are considered potential bioweapons. Botulinum neurotoxin type A is the most potent among the clostridial neurotoxins, and to date there is no post-exposure therapeutic intervention available. To develop inhibitors leading to drug design, it is imperative that critical interactions between the enzyme and the substrate near the active site are known. Although enzyme-substrate interactions at exosites away from the active site are mapped in detail for botulinum neurotoxin type A, information about the active site interactions is lacking. Here, we present the crystal structures of botulinum neurotoxin type A catalytic domain in complex with four inhibitory substrate analog tetrapeptides, viz. RRGC, RRGL, RRGI, and RRGM at resolutions of 1.6-1.8 A. These structures show for the first time the interactions between the substrate and enzyme at the active site and delineate residues important for substrate stabilization and catalytic activity. We show that OH of Tyr(366) and NH(2) of Arg(363) are hydrogen-bonded to carbonyl oxygens of P1 and P1' of the substrate analog and position it for catalytic activity. Most importantly, the nucleophilic water is replaced by the amino group of the N-terminal residue of the tetrapeptide. Furthermore, the S1' site is formed by Phe(194), Thr(215), Thr(220), Asp(370), and Arg(363). The K(i) of the best inhibitory tetrapeptide is 157 nm.     

Facing the global challenges posed by biological weapons

This review article examines the growing concern about the threat posed by the use of biological weapons by States or terrorist groups. The article analyzes the nature of the perceived risk from bioweapons, the historical attempts to control them, and the emerging policy and legal framework designed to deal with the bioweapon threat.     

军团菌研究进展

军团菌是一种革兰阴性致病菌,常污染水环境,引起人呼吸道急性感染,可作为生物战剂使用。由于军团菌病暴发范围广,且对人类健康构成了严重威胁,因此越来越受到人们的关注。我们简要综述其病原学、致病机制、实验室检测方法、流行病学和预防控制等方面的进展。     

Synthesis, topoisomerase I inhibition and antitumor cytotoxicity of 2,2':6',2"-, 2,2':6',3"- and 2,2':6',4"-terpyridine derivatives

For the development of new anticancer agents, 2,2':6',2"-, 2,2':6',3"- and 2,2':6',4"-terpyridine derivatives were designed and evaluated for their topoisomerase I inhibitory activity and antitumor cytotoxicity. Structure-activity relationship studies indicated that 2,2':6',2"-terpyridine derivatives were highly cytotoxic toward several human tumor cell lines, whereas 2,2':6',3"- and 2,2':6',4"-terpyridine derivatives were potent topoisomerase I inhibitors.     

Whole genome amplification--applications and advances

The concept of whole genome amplification is something that has arisen in the past few years as the polymerase chain reaction (PCR) has been adapted to replicate regions of genomes that are of biological interest. The applications are many--forensic science, embryonic disease diagnosis, bioterrorism genome detection, "immortalization" of clinical samples, microbial diversity, and genotyping. Several recent papers suggest that whole genomes can be replicated without bias or non-random distribution of the target, these findings open up a new avenue to molecular biology.     

Multi-pathogens sequence containing plasmids as positive controls for universal detection of potential agents of bioterrorism

Background  

The limited circulation of many of the agents that are likely to be used in a bioterrorism attack precludes the ready availability of positive controls. This means that only specialized laboratories can screen for the presence of these agents by nucleic amplification assays. Calibrated controls are also necessary for quantitative measurements. Primers and probes to be used in both conventional and real-time PCR assays were designed for the detection of agents likely to be used by a bioterrorist. Three plasmids, each of which contains 4 to 6 specific sequences from agents on the CDC Category A and B list (excluding RNA viruses) were constructed. Two plasmids incorporate the sequences of Category A and B agents, respectively. The third plasmid incorporates sequences from Variola major and organisms that cause rash-like illnesses that may be clinically confused with smallpox. An "exogenic sequence", introducing a NotI restriction site was incorporated in the native sequences of the bioterrorism agents inserted in plasmids. The designed molecular system for detection of bioterrorism agents was tested on each of these agents (except Monkeypox virus, Smallpox virus and 2 Burkholderia species for which no native DNA was available) and a collection of 50 isolates of C. burnetii using constructed plasmids as positive controls.