United States medical preparedness for nuclear and radiological emergencies

Abstract

With the end of the Cold War in 1991, U.S. Government (USG) investments in radiation science and medical preparedness were phased out; however, the events of 11 September, which involved a terroristic attack on American soil, led to the re-establishment of funding for both radiation preparedness and development of approaches to address injuries. Similar activities have also been instituted worldwide, as the global threat of a radiological or nuclear incident continues to be a concern. Much of the USG’s efforts to plan for the unthinkable have centred on establishing clear lines of communication between agencies with responsibility for triage and medical response, and external stakeholders. There have also been strong connections made between those parts of the government that establish policies, fund research, oversee regulatory approval, and purchase and stockpile necessary medical supplies. Progress made in advancing preparedness has involved a number of subject matter meetings and tabletop exercises, publication of guidance documents, assessment of available resources, clear establishment of anticipated concepts of operation for multiple radiation and nuclear scenarios, and identification/mobilization of resources. From a scientific perspective, there were clear research gaps that needed to be addressed, which included the need to identify accurate biomarkers and design biodosimetry devices to triage large numbers of civilians, develop decorporation agents that are more amenable for mass casualty use, and advance candidate products to address injuries caused by radiation exposure and thereby improve survival. Central to all these activities was the development of several different animal constructs, since efficacy testing of these approaches requires extensive work in research models that accurately simulate what would be expected in humans. Recent experiences with COVID-19 have provided an opportunity to revisit aspects of radiation preparedness, and leverage those lessons learned to enhance readiness for a possible future radiation public health emergency.

Biofluid Metabolomics of Mice Exposed to External Low-Dose Rate Radiation in a Novel Irradiation System, the Variable Dose-Rate External 137Cs Irradiator

“…Threats from large-scale radiological events necessitate development of radiation countermeasures, including rapid high-throughput biodosimetry. , Complex exposures from a potential ground-burst improvised nuclear device will include both higher dose rate and low-dose rate (LDR) ionizing radiation (IR) exposures from γ and neutron components . LDR IR exposure will consist of external contamination (groundshine) and radionuclide ingestion or inhalation, of particular concern being 137 Cs.…”

Radiation countermeasures for hematopoietic acute radiation syndrome: growth factors, cytokines and beyond

“…Since such agents will be administered to healthy individuals in anticipation to exposure, the FDA has stringent criteria for the approval of these agents. Pre-exposure drugs are specifically important for the use by the military and perhaps first responders during any large scale event (Gale 2017;Gale and Armitage 2018;DiCarlo et al 2021).…”

Biofluid Metabolomics and Lipidomics of Mice Exposed to External Very High-Dose Rate Radiation

“…Interestingly, levels of spermine showed higher fold increase at 7 d in the VHDR group (p < 0.001, VHDR FC = 6.3), which was not observed in the reference dose rate group. Several reports have implicated dysregulated metabolic conversion of spermidine to spermine or N 1 -acetylspermidine (see [29]), and it may be partially attenuated by deficient p53 activity [30] or age [31]. Perturbation to polyamine levels due to IR exposure is interesting, given the role of this pathway in DNA oxidation and apoptosis.…”

“…A set of coordinated terrorist attacks in the United States on 11 September 2001 led to the first renewed interest in establishing funding for ionizing radiation (IR) medical countermeasures and rapid testing for IR exposures since the time of the Cold War [1]. In addition to potential malicious attacks with improvised nuclear devices (INDs) or dirty bombs, we have since witnessed a nuclear accident at the Fukushima Daiichi Nuclear Power Plant in 2011 and attacks on Ukrainian nuclear power plants during a Russian invasion in 2022 that further highlight the need for high-throughput biodosimetry following IR exposures.…”