Priority to threats posed by plant toxins: management, detection, forensics and therapeutics in a bioterrorism incident taken to the next level – PLANT

Biological toxins are a focus of concern by public health and law enforcement on national and international levels due to the increasing threat of their deliberate release in a bioterrorist attack. Among these biological toxins the plant toxins ricin and abrin are of particular interest owing to their worldwide availability, ease of preparation, high morbidity and the lack of medical countermeasures. Over the last decade, they attracted much attention regarding criminal and terrorist misuse, culminating in the last-minute prevention of a bioterrorist attack using ricin in Cologne, DE, in 2018 which was preceded by similar terrorist activities in an earlier stage in France. Those biotoxin incidents challenged both countries: If a bioterrorist attack with ricin had occurred, public health and law enforcement would have been overwhelmed. There are no advanced management plans on how to respond to such a bioterrorist attack with ricin or abrin. On-site detection and laboratory confirmation has to be improved, methods for molecular forensics developed and new therapeutic approaches applied. The present project arises from discussions between first responders, special units and end users from public health and law enforcement in France and Germany (Direction Générale de la Police Nationale/DGPN; Bundeskriminalamt/BKA and Robert Koch-Institut/RKI) with scientific experts (Commissariat à l'énergie atomique et aux énergies alternatives/CEA and RKI) where gaps in preparedness and response to bioterrorism incidents with ricin and abrin were identified. We have built a project which starts from the requirements of first responders from public health and law enforcement being responsible for incident management after a deliberate release of ricin/abrin in a public building. To answer the first responders’ and authorities’ needs, we aim at optimizing our existing detection technologies including enzyme immunoassays, mass spectrometry, molecular biology and -omics technologies with potential for industrial exploitation. The approaches will be designed to be applied in a coherent detection and alert procedure including on-site detection and incident management, comprehensive laboratory confirmation and decontamination. A focus will be laid on molecular forensics which aims at providing yet not available information to identify perpetrators and stop subsequent attacks by precisely linking a biotoxin found at a scene to a source identified at a suspect based on unique, identifiable patterns characteristic for the agent. Targeting the current lack of medical countermeasures, we propose novel pharmacological agents for therapeutic intervention based on combination of antibodies and chemical drugs available and pre-tested in France and Germany. By combining the efforts in FR and DE in a synergistic approach, significant progress towards experimental drugs is expected including a concept for evaluation and provision of countermeasures in a case of a bioterrorist attack with ricin/abrin. A trusted scientific collaboration between the CEA and RKI in the field of CBRN (a former ANR-BMBF program and a current European project) will be the frame of the scientific proposal. By the involvement of first responders and special units from law enforcement and public health DGPN, FR, as well as BKA and RKI, DE, the established technologies and operating procedures will be evaluated in two final exercises highlighting the inter-operability of public health and law enforcement and covering essential steps in responding to a bioterrorism attack using plant toxins: management, detection, forensics and therapeutics.