Beyond the Dirty Dozen: A Proposed Methodology for Assessing Future Bioweapon Threats.

Background: Defense policy planners and countermeasure developers are often faced with vexing problems involving the prioritization of resources and efforts. This is especially true in the area of Biodefense, where each new emerging infectious disease outbreak brings with it questions regarding the causative agent's potential for weaponization. Recent experience with West Nile Virus, Severe Acute Respiratory Syndrome, Monkeypox, and H1N1 Influenza highlights this problem. Appropriately, in each of these cases, the possibility of bioterrorism was raised, although each outbreak ultimately proved to have a natural origin. In fact, determining whether an outbreak has an unnatural origin can be quite difficult. Thus, the questions remain: could the causative agents of these and other emerging infectious disease outbreaks pose a future weaponization threat? And how great is that threat? Should precious resources be diverted from other defense efforts in order to prepare for possible hostile employment of novel diseases by belligerents? Answering such critical questions requires some form of systematic threat assessment. Methods: Through extensive collaborative work conducted within NATO's Biomedical Advisory Council, we developed a scoring matrix for evaluating the weaponization potential of the causative agents of such diseases and attempted to validate our matrix by examining the reproducibility of data using known threat agents. Our matrix included 12 attributes of a potential weapon and was provided, along with detailed scoring instructions, to 12 groups of biodefense experts in 6 NATO nations. Study participants were asked to score each of these 12 attributes on a scale of 0-3: Infectivity, Infection-to-Disease Ratio (Reliability), Predictability (& Incubation Period), Morbidity & Mortality (Virulence), Ease of Large-Scale Production & Storage, Aerosol Stability, Atmospheric Stability, Ease of Dispersal, Communicability, Prophylactic Countermeasure Availability, Therapeutic Countermeasure Availability, and Ease of Detection. Reproducibility of scoring data was assessed by examining the standard deviations (SD) of mean scores. Results: Our results were unexpected. Several familiar biothreat diseases such as anthrax and tularemia were judged, by our experts, to be less threatening than many others owing to a number of factors including ease of detection, lack of communicability, and the ready availability of countermeasures. Conversely, several toxins were judged by experts to have very high potential as threat agents owing, in part, to their reliability, virulence, and a lack of available countermeasures. Agreement among experts, as determined by lower SD about a mean score, was greater for more familiar threats. Discussion: Our study was designed to provide a concise and east-to-apply set of criteria that could be used by NATO nations to evaluate emerging infectious disease threats with respect to their weaponization potential. Our results were unexpected. We believe that a lack of appropriate weighting factors may explain these results and suggest that future studies weigh each of the 12 proposed criteria based on the intended use of the assessment data and other situational factors. We believe that the greatest value of our study lies in a codification of the attributes of a biological weapon.

U.S. Department of Defense Multiple-Parameter Biodosimetry Network.

The U.S. Department of Defense (USDOD) service members are at risk of exposure to ionizing radiation due to radiation accidents, terrorist attacks and national defense activities. The use of biodosimetry is a standard of care for the triage and treatment of radiation injuries. Resources and procedures need to be established to implement a multiple-parameter biodosimetry system coupled with expert medial guidance to provide an integrated radiation diagnostic system to meet USDOD requirements. Current USDOD biodosimetry capabilities were identified and recommendations to fill the identified gaps are provided. A USDOD Multi-parametric Biodosimetry Network, based on the expertise that resides at the Armed Forces Radiobiology Research Institute and the Naval Dosimetry Center, was designed. This network based on the use of multiple biodosimetry modalities would provide diagnostic and triage capabilities needed to meet USDOD requirements. These are not available with sufficient capacity elsewhere but could be needed urgently after a major radiological/nuclear event.

Electron paramagnetic resonance radiation dose assessment in fingernails of the victim exposed to high dose as result of an accident.

In this paper, we report results of radiation dose measurements in fingernails of a worker who sustained a radiation injury to his right thumb while using 130 kVp X-ray for nondestructive testing. Clinically estimated absorbed dose was about 20-25 Gy. Electron paramagnetic resonance (EPR) dose assessment was independently carried out by two laboratories, the Naval Dosimetry Center (NDC) and French Institut de Radioprotection et de Sûreté Nucléaire (IRSN). The laboratories used different equipments and protocols to estimate doses in the same fingernail samples. NDC used an X-band transportable EPR spectrometer, e-scan produced by Bruker BioSpin, and a universal dose calibration curve. In contrast, IRSN used a more sensitive Q-band stationary spectrometer (EMXplus) with a new approach for the dose assessment (dose saturation method), derived by additional dose irradiation to known doses. The protocol used by NDC is significantly faster than that used by IRSN, nondestructive, and could be done in field conditions, but it is probably less accurate and requires more sample for the measurements. The IRSN protocol, on the other hand, potentially is more accurate and requires very small amount of sample but requires more time and labor. In both EPR laboratories, the intense radiation-induced signal was measured in the accidentally irradiated fingernails and the resulting dose assessments were different. The dose on the fingernails from the right thumb was estimated as 14 ± 3 Gy at NDC and as 19 ± 6 Gy at IRSN. Both EPR dose assessments are given in terms of tissue kerma. This paper discusses the experience gained by using EPR for dose assessment in fingernails with a stationary spectrometer versus a portable one, the reasons for the observed discrepancies in dose, and potential advantages and disadvantages of each approach for EPR measurements in fingernails.

Q-band electron paramagnetic resonance dosimetry in tooth enamel: biopsy procedure and determination of dose detection limit.

High-frequency Q-band (37 GHz) electron paramagnetic resonance (EPR) dosimetry allows to perform fast (i.e., measurement time <15 min) dose measurements using samples obtained from tooth enamel mini-biopsy procedures. We developed and tested a new procedure for taking tooth enamel biopsy for such dose measurements. Recent experience with EPR dose measurements in Q-band using mini-probes of tooth enamel has demonstrated that a small amount of tooth enamel (2-10 mg) can be quickly obtained from victims of a radiation accident. Accurate dose assessments can further be carried out in a very short time to provide important information for medical treatment. Here, the Q-band EPR dose detection limit for 5 and 10 mg samples is estimated to be 367 and 248 mGy, respectively. These values are comparable to the critical parameters determined for conventional X-band EPR in tooth enamel.

Study of the stability of EPR signals after irradiation of fingernail samples.

Previous studies have suggested that the electron paramagnetic resonance in fingernails can be used for radiation dosimetry purposes. Use of fingernails as an emergency dosimeter has benefits of easy, noninvasive sampling and fast dose measurements (∼10 min) potentially in field conditions and almost immediately after an exposure event. This study represents the next step in the development of EPR fingernail dosimetry; e.g., evaluation of the stability of the radiation-induced signal (RIS) at different storage and irradiation conditions. RIS fading during storage in both stressed (untreated) and unstressed (soaked in water) samples (n = 20) was studied at two temperature conditions: freezing (temp ≈ -20°C) and room temperature (20-24°C). Fingernail samples with the same clipping size and number and irradiated to 15 and 20 Gy were measured for over 200 d. Those irradiated to 100 and 200 Gy were measured for 114 d. The other group of samples irradiated to 1, 3, 8, and 20 Gy was followed for 25 mo of storage time. This study demonstrated that all samples that were kept at low freezing temperatures showed a stable RIS with no significant fading. All samples that were kept at room temperatures showed an initial fading of the signal with a slow rise of the EPR signal after irradiation with time to a saturation level. Obtained results allow making recommendations on the appropriate storage conditions of fingernails for EPR dosimetry use.

Fingernail dosimetry: current status and perspectives.

A summary of recent developments in fingernail EPR dosimetry is presented in this paper. Until 2007, there had been a very limited number of studies of radiation-induced signals in fingernails. Although these studies showed some promising results, they were not complete with regard to the nature of non-radiation signals and the variability of dose dependence in fingernails. Recent study has shown that the two non-radiation components of the EPR spectrum of fingernails are originated from mechanical stress induced in the samples at their cut. The mechanical properties of fingernails were found to be very similar to those of a sponge; therefore, an effective way to eliminate their mechanical deformation is by soaking them in water. Stress caused by deformation can also significantly modify the dose response and radiation sensitivity. Consequently, it is critically important to take into account the mechanical stress in fingernail samples under EPR dose measurements. Obtained results have allowed formulating a prototype of a protocol for dose measurements in human fingernails.