Deliberate Misuse Research Articles

Evaluation of Vaccines and Therapeutics Against Marburg Virus in Nonhuman Primate Models.

Marburg virus (MARV) has caused sporadic outbreaks of severe hemorrhagic fever in Africa in humans and nonhuman primates (NHPs) and has the potential to be used as a biological weapon. Currently, there are no licensed vaccines or therapeutics to respond to outbreaks or deliberate misuse. Vaccine and therapeutic efficacy testing against MARV requires animal models that accurately mimic human disease. In vitro testing in cell culture cannot appropriately model the complex immunological host responses required to accurately predict efficacy in humans, which will ultimately be required for licensure of a medical countermeasure (MCM). While small animal models for MARV have been valuable for dissecting disease processes and the screening of vaccine and drug candidates, there are several caveats to their use including required adaptation of the virus, lack of host-specific reagents, or the need of an immunocompromised host. Conversely, the NHP MARV disease model addresses all shortcomings of small animal models and closely recapitulates all hallmark features of human disease. As such, NHPs have served as the "gold standard" for testing filovirus MCMs and will most likely be required for regulatory approval. Here, we describe the use of NHPs for vaccine and therapeutic evaluation against MARV.

Virulence of Burkholderia pseudomallei ATS2021 Unintentionally Imported to United States in Aromatherapy Spray.

In the United States in 2021, an outbreak of 4 cases of Burkholderia pseudomallei, the etiologic agent of melioidosis and a Tier One Select Agent (potential for deliberate misuse and subsequent harm), resulted in 2 deaths. The causative strain, B. pseudomallei ATS2021, was unintentionally imported into the United States in an aromatherapy spray manufactured in India. We established that ATS2021 represents a virulent strain of B. pseudomallei capable of robust formation of biofilm at physiologic temperatures that may contribute to virulence. By using mouse melioidosis models, we determined median lethal dose estimates and analyzed the bacteriologic and histopathologic characteristics of the organism, particularly the potential neurologic pathogenesis that is probably associated with the bimABm allele identified in B. pseudomallei strain ATS2021. Our data, combined with previous case reports and the identification of endemic B. pseudomallei strains in Mississippi, support the concept that melioidosis is emerging in the United States.

The whack-a-mole governance challenge for AI-enabled synthetic biology: literature review and emerging frameworks.

AI-enabled synthetic biology has tremendous potential but also significantly increases biorisks and brings about a new set of dual use concerns. The picture is complicated given the vast innovations envisioned to emerge by combining emerging technologies, as AI-enabled synthetic biology potentially scales up bioengineering into industrial biomanufacturing. However, the literature review indicates that goals such as maintaining a reasonable scope for innovation, or more ambitiously to foster a huge bioeconomy do not necessarily contrast with biosafety, but need to go hand in hand. This paper presents a literature review of the issues and describes emerging frameworks for policy and practice that transverse the options of command-and-control, stewardship, bottom-up, and laissez-faire governance. How to achieve early warning systems that enable prevention and mitigation of future AI-enabled biohazards from the lab, from deliberate misuse, or from the public realm, will constantly need to evolve, and adaptive, interactive approaches should emerge. Although biorisk is subject to an established governance regime, and scientists generally adhere to biosafety protocols, even experimental, but legitimate use by scientists could lead to unexpected developments. Recent advances in chatbots enabled by generative AI have revived fears that advanced biological insight can more easily get into the hands of malignant individuals or organizations. Given these sets of issues, society needs to rethink how AI-enabled synthetic biology should be governed. The suggested way to visualize the challenge at hand is whack-a-mole governance, although the emerging solutions are perhaps not so different either.

“That is just your stuff”: The potential use and abuse of congruence in counselling and psychotherapy practice and training

AbstractThis piece discusses the potential use and misuse of congruence within counselling training and practice. A definition of congruence is provided, and how deliberate misuse of congruence could result from two separate emotional communications (bullying and gaslighting) is discussed. Current representations and misrepresentations of congruence in counselling and psychotherapy have been highlighted. A new term of “Intentional Congruence Misuse” was coined to explain this position (not to be confused with incongruence). “Intentional Congruence Misuse” is the deliberate bullying of another individual using terms related to congruence. A discussion has been provided to emphasise the evident implications for counselling, psychotherapy practice and training. The author acknowledges that this opinion piece will be from a biased perspective. Still, it does not aim to detract from others who have found their therapy and counselling training beneficial.

Assessing high fidelity multi-component models to facilitate safeguards at Gas Centrifuge Enrichment Plants

The International Atomic Energy Agency (IAEA) inspectors routinely carry out environmental sampling (ES) as a verification method. Collection of environmental swipe samples at various locations in Gas Centrifuge Enrichment Plants (GCEPs) is an important process in detecting misuse of a declared facility and possibly the existence of undeclared nuclear material. These samples are measured for isotopic composition in uranium containing particles by Thermal Ionization Mass Spectrometry (TIMS) or Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Even though ES is highly effective in detecting the absolute value of enrichments and their deviations from the declared values, it cannot explain the cause of those changes. Several potential explanations can serve as possibilities for particles detected above or other than the declared enrichment. These include normal and non-malicious events such as the design of the enrichment cascades, unintentional failures of the machines, or overshoot during startup of a cascade. It can also be the result of deliberate misuse by the facility operators. The primary objective of this work is to understand how these factors affect the enrichments produced by a cascade and quantify anticipated multi-isotopic concentrations for each case. The following methodology is employed to determine signatures at a particular facility.1)Utilize a new two-dimensional multi-component diffusion code to obtain centrifuge performance data and use that information to design and perform cascade analysis. Compare and contrast the results with previous 1-D radially averaged solutions from the Pancake code.2)Design a GCEP cascade with the production goal of 19.75% 235U for each set of machine data above. Investigate two cascade scenarios that include enrichment of natural uranium (NU) feed to 19.75% 235U in a single cascade compared to a two-step process of NU to 5% and then 5% to 19.75%.3)Simulate the intentional vs unintentional off-normal scenarios in the cascades to assess the differences in isotopic concentrations.A non-ideal squared-off cascade model developed at the University of Virginia is used to calculate flow rates and isotopic concentrations of the process gas. The analysis is performed using the Rome machine model operated at 600 m/s rotor speed. The upper and lower bounds of normal and abnormal enrichments in a typical facility are used in conjunction with ES results to understand the root causes of such observations.

Secure Automatic Identification System (SecAIS): Proof-of-Concept Implementation

The automatic identification system (AIS), despite its importance in worldwide navigation at sea, does not provide any defence mechanisms against deliberate misuse, e.g., by sea pirates, terrorists, business adversaries, or smugglers. Previous work has proposed an international maritime identity-based cryptographic infrastructure (mIBC) as the foundation upon which the offer of advanced security capabilities for the conventional AIS can be built. The proposed secure AIS (SecAIS) does not require any modifications to the existing AIS infrastructure, which can still be used for normal operations. Security-enhanced AIS messages enjoying source authentication, encryption, and legitimate pseudo-anonymization can be handled on an as-needed basis. This paper reports on a proof-of-concept implementation of the SecAIS. Specifically, we report on the implementation of the SecAIS over an mIBC founded on the RFC6507 (ECCSI) and the RFC6508 (SAKKE) standards, and we discuss the results of performance tests with this implementation. The tests indicate that the SecAIS is a feasible solution that does not affect the conventional AIS infrastructure and has an affordable operational cost.

Going Beyond Deterrence: A Middle-Range Theory of Motives and Controls for Insider Computer Abuse

Reports indicate that employees are willing to share sensitive information under certain circumstances, and one-third to half of security breaches are tied to insiders. These statistics reveal that organizational security efforts, which most often rely on deterrence-based sanctions to address the insider threats to information security, are insufficient. Thus, insiders’ computer abuse (ICA)—unauthorized and deliberate misuse of organizational information resources by organizational insiders—remains a significant issue for industry. We present a motive–control theory of ICA that distinguishes among instrumental and expressive motives and internal and external controls. Specifically, we show that organizational deterrents (e.g., sanctions) do not create motives for ICA, but weaken existing motives (e.g., financial benefits). Conversely, financial benefits and psychological contract violations create motives to perform ICA, and insiders’ self-control diminishes the influence of these motives. The implications for practice are threefold: (1) organizations should make efforts to reduce psychological contract breach for employees by increasing the congruence between expectations and reality to reduce expressive motives for ICA; (2) organizations should seek maintain personnel with adequate self-control to diminish the impact of harmful ICA motives should they arise; and (3) organizations should develop targeted sanctions for committing ICA to control the harmful influence of financial motives.

Use of X-rays to prevent transfusion-induced graft-versus-host disease

Transfusion associated graft versus host disease (TA-GvHD) is a rare complication of transfusion treatment with blood products containing viable lymphocytes. The risk of developing TA-GvHD depends on number and sustainability of lymphocytes in blood product, host’s immune system reactivity and the difference in human leukocyte antigen (HLA) system between donor and recipient. Standard method of TA-GvHD prevention is irradiation of blood products with ionizing radiation and absorbed dose of 25-50 Gy. The aim of irradiation is inactivation of viable lymphocytes in blood product containing cells (red blood cells, platelets, granulocytes) and lymphocyte proliferation inhibition in blood product recipient. In the last two decades, gamma irradiation has been extensively abandoned and replaced with specially designed cabinet machines using X-ray irradiation which are suitable for hospital and blood bank use. This reduces the risk of accidental or deliberate misuse of radioactive source, solves radioactive waste disposal issues and reduces ionizing irradiation exposure of employees in blood establishments. In Blood Bank of Croatian Institute of Transfusion Medicine, X-ray irradiation of blood products has been carried out since 2014 with a year rate of 20,000 irradiated cell blood products used in treatment of patients at risk of developing TA-GvHD.

Biosecurity in an age of open science.

The risk of accidental or deliberate misuse of biological research is increasing as biotechnology advances. As open science becomes widespread, we must consider its impact on those risks and develop solutions that ensure security while facilitating scientific progress. Here, we examine the interaction between open science practices and biosecurity and biosafety to identify risks and opportunities for risk mitigation. Increasing the availability of computational tools, datasets, and protocols could increase risks from research with misuse potential. For instance, in the context of viral engineering, open code, data, and materials may increase the risk of release of enhanced pathogens. For this dangerous subset of research, both open science and biosecurity goals may be achieved by using access-controlled repositories or application programming interfaces. While preprints accelerate dissemination of findings, their increased use could challenge strategies for risk mitigation at the publication stage. This highlights the importance of oversight earlier in the research lifecycle. Preregistration of research, a practice promoted by the open science community, provides an opportunity for achieving biosecurity risk assessment at the conception of research. Open science and biosecurity experts have an important role to play in enabling responsible research with maximal societal benefit.

Strengthening biological security after COVID-19: Using cartoons for engaging life science stakeholders with the Biological and Toxin Weapons Convention (BTWC)

The devastating effects of the COVID-19 pandemic have acutely shown the need for maintaining robust international and national systems for biological security and ensuring that life sciences are used only for peaceful purposes. Life science stakeholders can play an important role in safeguarding scientific and technological advances in biology and related fields against accidental or deliberate misuse, not least because they are on the frontlines of driving innovation. In this paper, we argue that enhancing awareness and understanding of the risk of deliberate disease is essential for effective biological security. We first discuss the issue of ‘dual use’ in science and technology as it relates to disarmament and non-proliferation of weapons of mass destruction. Second, we review how scientist engagement with dual-use risks has been addressed in the context of the Biological and Toxin Weapons Convention (BTWC). Third, we report on the development of an innovative awareness-raising tool, a cartoon series, that can be used for engaging life science stakeholders with BTWC issues. Finally, we outline a set of practical considerations for promoting sustainable life science engagement with the BTWC.

Biorisk Management for SARS-CoV-2 Research in a Biosafety Level-3 Core Facility.

The emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents hazards to researchers and other laboratory personnel in research settings where the live virus is stored and handled. The Biosafety Level-3 (BSL-3) Core Facility (CF) at Yong Loo Lin School of Medicine in National University of Singapore (NUS Medicine) has implemented a biorisk management (BRM) system to ensure that biorisk to employees, the public, or the environment are consistently minimized to an acceptable level while working with SARS-CoV-2. This chapter summarizes how a BRM system can be implemented in academic institutions based on international standards in the context of existing local legislations/regulations and institutional policies/guidelines to minimize the risk of laboratory-acquired infections and deliberate misuse of the newly emerged virus, SARS-CoV-2 in BSL-3 laboratories. The BRM programs prioritize performing risk assessments prior to implementation of work processes and reassessing the risk portfolio of the facilities from time to time, determining root causes and prevention of recurrences. Focusing on awareness-raising and educating the laboratory users in biosafety and biosecurity, and identifying opportunities for improvement are the other key factors for a sustainable and successful BRM system in the NUS Medicine BSL-3 CF.

A machine learning toolkit for genetic engineering attribution to facilitate biosecurity

The promise of biotechnology is tempered by its potential for accidental or deliberate misuse. Reliably identifying telltale signatures characteristic to different genetic designers, termed ‘genetic engineering attribution’, would deter misuse, yet is still considered unsolved. Here, we show that recurrent neural networks trained on DNA motifs and basic phenotype data can reach 70% attribution accuracy in distinguishing between over 1,300 labs. To make these models usable in practice, we introduce a framework for weighing predictions against other investigative evidence using calibration, and bring our model to within 1.6% of perfect calibration. Additionally, we demonstrate that simple models can accurately predict both the nation-state-of-origin and ancestor labs, forming the foundation of an integrated attribution toolkit which should promote responsible innovation and international security alike.

Withdrawal and Misuse Concerns of Consumers regarding Opioid Analgesic and Anxiolytic, Hypnotic and Sedative Medicines

Background Opioid analgesic (OA) and anxiolytic, hypnotic and sedative (AHS) medicines use raise community concerns about risks of dependence: dose escalation, unintentional misuse. Objectives: We aimed to identify common consumer OA and AHS information gaps and concerns that led to information seeking from a hotline. Methods: We conducted a retrospective, mixed-method observational study of consumers’ OA and AHS-related calls to an Australian national medicines call center (September 2002-30 June 2010). We analyzed these medicines’ call characteristics compared to their respective rest of calls (ROC) and thematically explored narratives concerning withdrawal and misuse. Results: Of 123,217 calls, 7,395 (6.0%) involved OA and 7,789 (6.2%) AHS, with consistency between call characteristics. While female middle-aged callers predominated, more males called for these medicines than their complementary ROC. Uncertainty about unresolved OA and AHS concerns led to help-seeking that was consistent over eight years. Main motivations were inadequate information (OA 44.5%; AHS 41.2%), seeking a second opinion (OA 24.2%; AHS 24.2%), worrying symptoms (OA 21.6%; AHS 23.1%), and conflicting information (OA 4.9%; AHS 5.1%). Callers focused on withdrawal and issues related to inadvertent overuse or deliberate misuse (OA 9.2% vs. non-OA ROC 2.9%; AHS 12.6% vs. non-AHS ROC 2.7%). Primary themes were similar for both cohorts: concern about harm or aiming to minimize harm by information seeking, requesting a strategy, or reassurance. Conclusions: Consumers have under-recognized perceptions of harm from OA and AHS use, particularly withdrawal and misuse. Resources based on real world consumer concerns can encourage open dialogue between patients and their prescribers.

Drug Development against Smallpox: Present and Future.

Forty years after the last endemic smallpox case, variola virus (VARV) is still considered a major threat to humans due to its possible use as a bioterrorism agent. For many years, the risk of disease reemergence was thought to solely be through deliberate misuse of VARV strains kept in clandestine laboratories. However, recent experiments using synthetic biology have proven the feasibility of recreating a poxvirus de novo, implying that VARV could, in theory, be resurrected. Because of this new perspective, the WHO Advisory Committee on VARV Research released new recommendations concerning research on poxviruses that strongly encourages pursuing the development of new antiviral drugs against orthopoxviruses. In 2018, the U.S. FDA advised in favor of two molecules for smallpox treatment, tecovirimat and brincidofovir. This review highlights the difficulties to develop new drugs targeting an eradicated disease, especially as it requires working under the FDA "animal efficacy rule" with the few, and imperfect, animal models available.

Public awareness, acceptability and risk perception about infectious diseases dual-use research of concern: a cross-sectional survey

ObjectivesIn this study, we aimed to measure the awareness, acceptability and perceptions of current issues in biosecurity posed by infectious diseases dual-use research of concern (DURC) in the community. DURC...

Biological warfare: the history of microbial pathogens, biotoxins and emerging threats

Bioterrorism is the deliberate misuse of a pathogen (virus, bacterium or other disease-causing microorganisms) or biotoxin (poisonous substance produced by an organism) to cause illness and death amongst the population. Bioterrorism and biological warfare (biowarfare) are terms often used interchangeably. However, bioterrorism is typically attributed to the politically motivated use of biological weapons by a rogue state, terrorist organisation or rogue individual whereas biological warfare refers to a country’s use of bioweapons. Although rare, bioterrorism is a rapidly evolving threat to global security due to significant advancements in biotechnology in recent years and the severity of agents that could be exploited. The pursuit of publicity plays a vital role in bioterrorism. The success of a biological attack is often calculated by the extent of terror resulting from the event, psychological disruption of society and political breakdown, rather than the lethal effects of the agent used.

Multi-Dimensional Fraud Detection Metrics in Business Processes and their Application

Occupational fraud is defined as the deliberate misuse of one’s occupation for personal enrichment. It poses a significant challenge for organizations and governments. Estimates indicate that the funds involved in occupational fraud cases investigated across 125 countries between 2018 and 2019 exceeded US$3.6 billion. Process-based fraud (PBF) is a form of occupational fraud that is perpetrated inside business processes. Business processes underlie the logic of the work that organizations undertake, and they are used to execute an organization’s strategies to achieve organizational goals. Business processes should be examined for potential fraud risks to ensure that businesses achieve their objectives. While it is impossible to prevent fraud entirely, it must be detected. However, PBF detection metrics are not well developed at present. They are scattered, unstandardized, not validated, and, in some cases, absent. This study aimed to develop a comprehensive PBF detection metric by leveraging and operationalizing a taxonomy of fraud detection metrics for business processes as an underlying theory. 41 PBF detection metrics were deduced from the taxonomy using design science research. To evaluate their utility, the application of the metrics was undertaken using illustrative scenarios, and a real example of the implementation of the metrics was provided. The developed metrics form a complete, classified, validated, and standardized list of PBF detection metrics, which include all the necessary PBF detection dimensions. It is expected that the stakeholders involved in PBF detection will use the metrics established in this work in their practice to increase the effectiveness of the PBF detection process.

Video Data for Escalator Accidents

Many videos of escalator accidents are available on social media, especially YouTube. A review of a large sample of such videos reveals information about some types of accidents not readily found or well described in hospital reports and behavioral observations. These include numerous deliberate misuse modes such as sliding or riding on handrails, as well as risky activity such as wearing clothes that can become entangled in the mechanism and traveling in the wrong direction, and various mechanical problems. Advantages and limitations of video data are discussed, along with suggestions for possible safety interventions.

Identifying Medical Equipment Usability Issues from Social Media Reports

Traditional methods of investigating usability include usability tests, heuristic evaluations, surveys, and field methods. User self-reports of equipment problems such as through the FDA MAUDE database are also available, but there may be limited information reported. Often, people turn to social media to share stories and learn from others. In this study, the authors explored using social media as a means of identifying possible usability issues with medical devices and products. As a proof of concept, the authors focused on insulin pumps, continuous glucose monitors, and sleep apnea machines. Reports of medical equipment use issues were grouped into three categories: 1) correct instructions for product use, 2) apparently inadvertent incorrect instructions for use and 3) instructions that encouraged or could promote deliberate misuse. Each of these has different implications for designers, clinical product review committee members, and clinicians.

Development of a Biosecurity Checklist for Laboratory Assessment and Monitoring.

Introduction:Laboratory biosecurity is of continuously growing interest due to increasing concerns about deliberate misuse of biological materials and emerging biological risks. These risks continue to be magnified by globalization, the rapid pace of scientific development, and dual-use technologies. Worldwide laboratory capacities are expanding, which calls for concrete actions to improve laboratory biosafety and biosecurity practices to protect researchers and the community. Hence, laboratories require comprehensive biorisk management programs to minimize the risk of accidental and deliberate release of infectious biological materials.Objective:Malaysia has prioritized the concern of national biosecurity and aims to consolidate laboratory biosecurity performance to detect and prevent the deliberate release of biological agents.Methods:Two 3-day workshops were organized over the course of four months in which Malaysia collaborated with The Netherlands. This bilateral engagement aimed to integrate biosecurity practices in their national biorisk management programs, and resulted into a comprehensive biosecurity checklist for laboratory assessment and monitoring.Results:This biosecurity checklist is based on Malaysian and Dutch expert opinions and national and international guidelines and regulations. The biosecurity checklist is a survey-driven tool that consists of a set of concrete questions for each key biosecurity area, which are discussion points for assessment.Conclusion:We display a practical biosecurity checklist for laboratory assessment and monitoring. Although the presented checklist was the template for the specific Malaysia checklist, it could serve as a template for other countries.