Pattern of bioterrorism in ancient times: lessons to be learned from the microbial and toxicological aspects.

The current research aimed to analyze the history of bioterrorism in antiquity and to adapt the data to modern medical knowledge. To this end, a thorough evaluation of the literature related to the ancient history of bioterrorism and modern data was done using the Web of Sciences, Science Direct, Scopus, PubMed, and Google Scholar. Results showed that knowledge of bioterrorism has existed since antiquity in different civilizations. Biological and toxicological agents were used as an instrument of legal execution, as a warfare tool in battles, or to eliminate political rivals across nations. Ancient people researched bioterrorism to apply it against enemies and at the same time provide countermeasures in favor of themselves and allies. Despite the existence of the principles of bioterrorism since ancient times, adaptation of the data to modern research can assist in planning countermeasure efforts, preventive actions, and treatments in the framework of modern counterterrorism medicine.

From Squirrels to Biological Weapons: The Early History of Tularemia.

After George McCoy accidentally discovered a new infection in 1911 while investigating bubonic plague in squirrels, he transmitted the disease to experimental animals and isolated the causative organism. He called it Bacterium tularense, after Tulare County, California. In 1919, Edward Francis determined that an infection called "deer-fly fever" was the same disease, naming it "tularemia." He demonstrated that it occurred in wild rabbits and inadvertently showed that it was highly infectious, for he and all his laboratory assistants contracted the illness. This characteristic led to studies of its potential as a biological weapon, including involuntary human experimentation by Japan among civilian, political and military prisoners, and its probable use in warfare during World War II. Later, in the United States, voluntary human experimentation occurred in the 1950s-1960s with penitentiary inmates and non-combatant soldiers. Soviet Union scientists allegedly developed a vaccine-resistant strain, which they tested as a biological weapon in 1982-1983.

Rift Valley fever in animals and humans: Current perspectives.

Rift Valley fever (RVF) is an ecologically complex emerging arboviral disease that causes significant illness in both livestock and people. This review article is designed to assist the reader in understanding the varied aspects of RVF disease in animals and humans. The historical facets of RVF disease, including the evolution of human outbreaks, are presented and discussed. The different clinical presentations of human RVF disease and the underlying causes are then addressed. We explore the exposure and transmission potential of RVF in animals and people. In the concluding section, we discuss the historical role of RVF as a biological weapon. We conclude with an outline of the important unanswered questions for ongoing research into this important zoonotic disease.

Yesterday and Today: The Impact of Research Conducted at Camp Detrick on Botulinum Toxin.

Introduction: This review summarizes the research conducted on botulinum toxin (BoTx) from 1943 to 1956 by a small group of Camp Detrick investigators and their staff. A systematic, cross-disciplinary approach was used to develop effective vaccines against this biological warfare threat agent. In response to the potential need for medical countermeasures against BoTx during World War II, the refinement of isolation and purification techniques for BoTx successfully led to the large-scale production of botulinum toxoid vaccines. In addition, the work at Camp Detrick provided the foundation for the subsequent use of BoTx as a tool for studying the trophic regulation of skeletal muscle within motor neuron terminals and, more recently, for elucidation of the intricate details of neurotransmitter release at the molecular level. Indirectly, Camp Detrick investigators also played a significant role in studies that culminated in the use of BoTx as a pharmaceutical product that has been approved by the U.S. Food and Drug Administration for treating movement disorders, autonomic dysfunctions, and other conditions. Methods: Online literature searches were performed with Google, Google Scholar, PubMed, the bibliography from the Camp Detrick technical library, and at the Defense Technical Information Center. Reference lists in some of the primary research publications and reviews also provided source material. Search terms included botulinum, botulinus, and Camp Detrick. References related to the subsequent impacts of the Camp Detrick results were selected and cited from reviews and primary references in the more recent literature. Notes on toxin nomenclature and potential sources of error in this study are presented. Results: The literature searches returned 27 citations of Camp Detrick authors, 24 of which were articles in peer-reviewed journals. The publications by these investigators included several disciplines such as biochemistry, immunology, pharmacology, physiology, and toxicology. A fundamental finding was the identification of critical nutritional components for improved growth of Clostridium botulinum and the increased production of BoTx serotype A. The purification processes that were developed at Camp Detrick allowed for the production of crystalline material to be scaled up for the manufacture of toxoid vaccine. Based on the research by Camp Detrick scientists, a toxoid supply of over 1 million units was available to vaccinate ~300,000 troops before the large-scale operations of D-Day. Conclusions: BoTx research during the period 1943 to 1956 resulted in refinements in the techniques for isolating and purifying the crystalline BoTx type A. These results led to the development and manufacture of a toxoid vaccine that was available in a sufficient quantity to protect ~300,000 warfighters in a large-scale military operation. One of the most important long-term consequences derived from the knowledge gained by the efforts at Camp Detrick was the development in the 1980s of safe and effective therapeutic uses for BoTx type A, the most lethal biological substance known.

The History of Biological Weapons Use: What We Know and What We Don't.

This article critically reviews the literature on the history of biological warfare, bioterrorism, and biocrimes. The first serious effort to review this entire history, made in 1969, had numerous limitations. In recent decades, several authors have filled many of the gaps in our understanding of the past use of biological agents (including both pathogens and toxins), making it possible to reconstruct that history with greater fidelity than previously possible. Nevertheless, there are numerous remaining gaps, and closer inspection indicates that some supposed uses of biological weapons never took place or are poorly substantiated. Topics requiring additional research are identified.

[The experiments conducted by Japanese on human guinea pigs, and the use of biological weapons during the Sino-Japanese war (1937-1945)]. / Gli esperimenti su cavie umane effettuati dai giapponesi e l'utilizzo delle armi biologiche nel teatro di guerra cino-giapponese (1937-1945)

Starting from the end of the nineteenth century, and during the first four decades of the past century, Japan showed considerable military expansion, on the back of a pan-Asiatic and imperialistic ideology, comparable only to those expressed by Wilhelmian and Nazi Germany. This growth led to Japan playing an extremely important role in the Asia-Pacific continent, which unavoidably brought the country onto a collision course with the British Empire and the United States of America. The Japanese general Shiro Ishii, who had undoubted organisational abilities but also a propensity for crimes against mankind, starting from the end of the 1920s and during the subsequent decade, under the suggestion of a military physician, developed a research programme to obtain biological weapons, since he was aware of the lack of raw materials, technology and scientific background in nuclear weapons. This project was taken forward despite Japan's ratification of the Geneva protocol, undersigned by 70 nations, which posed strict limits to the use of both biological and chemical weapons. In actual fact, the protocol allowed these weapons for defensive purposes, and permitted their experimental development. The research programme, developed with the support of the high command of the Japanese army and certainly known by the Emperor (Tenno) Hirohito, had its operative basis from the year 1932 in the satellite state of Manchukuo, but later and paralleling the increased, aggressive behaviour towards China and the English and American colonies during World War II, spread towards other Asian provinces occupied by the Japanese armies, with other operative units. In these dedicated bases, which were true concentration camps, numerous experiments were carried out on human guinea pigs, frequently concluding with vivisection. Among others, experiments of freezing, thirst, hunger, loss of blood, wounding with firearms, and bone fractures, were performed, as well as the inoculation of microorganisms (including Yersinia pestis, Vibrio cholerae, Richettsia typhi, and Salmonella typhi), and spores of Bacillus anthracis. With regard to infectious diseases, the objective was to establish the most effective models for the use of biological weapons, taking into consideration the features of territories and populations to be placed under attack. It has been estimated that over 100,000 people suffered in such experiments, and according to the authors who studied these facts on the basis of original documentation, approximately 540,000 subjects lost their lives in China and Korea due to epidemics caused by the Japanese between 1937 and 1945.

Overall view of chemical and biochemical weapons.

This article describes a brief history of chemical warfare, which culminated in the signing of the Chemical Weapons Convention. It describes the current level of chemical weapons and the risk of using them. Furthermore, some traditional technology for the development of chemical weapons, such as increasing toxicity, methods of overcoming chemical protection, research on natural toxins or the introduction of binary technology, has been described. In accordance with many parameters, chemical weapons based on traditional technologies have achieved the limit of their development. There is, however, a big potential of their further development based on the most recent knowledge of modern scientific and technical disciplines, particularly at the boundary of chemistry and biology. The risk is even higher due to the fact that already, today, there is a general acceptance of the development of non-lethal chemical weapons at a technologically higher level. In the future, the chemical arsenal will be based on the accumulation of important information from the fields of chemical, biological and toxin weapons. Data banks obtained in this way will be hardly accessible and the risk of their materialization will persist.

From biodefence to biosecurity: the Obama administration's strategy for countering biological threats.

The Seventh Review Conference of the Biological Weapons Convention (BWC), the first international treaty to outlaw an entire class of weapons, was held in Geneva in December 2011. On 7 December, Secretary of State Hillary Clinton became the highest-ranking US government official to address a BWC meeting. Secretary Clinton told the assembled delegation that 'we view the risk of bioweapons attack as both a serious national security challenge and a foreign policy priority'. At the same time, she warned that a large-scale disease outbreak 'could cripple an already fragile global economy'. Secretary Clinton's speech reflected a new understanding that the range of biological threats to international security has expanded from state-sponsored biological warfare programmes to include biological terrorism, dual-use research and naturally occurring infectious diseases such as pandemics. Recognizing these changes, President Barack Obama released a new national strategy for countering biological threats in 2009. This strategy represents a shift in thinking away from the George W. Bush administration's focus on biodefence, which emphasized preparing for and responding to biological weapon attacks, to the concept of biosecurity, which includes measures to prevent, prepare for and respond to naturally occurring and man-made biological threats. The Obama administration's biosecurity strategy seeks to reduce the global risk of naturally occurring and deliberate disease outbreaks through prevention, international cooperation, and maximizing synergies between health and security. The biosecurity strategy is closely aligned with the Obama administration's broader approach to foreign policy, which emphasizes the pragmatic use of smart power, multilateralism and engagement to further the national interest. This article describes the Obama administration's biosecurity strategy; highlights elements of continuity and change from the policies of the Bush administration; discusses how it fits into Obama's broader foreign policy agenda; and analyses critical issues that will have to be addressed in order to implement the strategy successfully.

Bioética e armas biológicas no contexto internacional / Bioethics and biological weapons in the international context

O estudo "Bioética e Armas Biológicas no Contexto Internacional" investiga a aplicação de análise sob a ótica da bioética de intervenção a diálogos internacionais no âmbito de um sistema de estados. O estudo de caso testa o método de investigação que consiste na identificação de valores e posicionamentos contratantes entre países desenvolvidos e em desenvolvimento e suas possibilidades de incorporação a regras, normas e regulações adotadas pela comunidade internacional. Nesse processo é verificado o equilíbrio de oportunidades entre países do Norte e do Sul para inserirem suas necessidades e interesses nas normas de convivência entre Estados como indicativo das condições de justiça e equidade no âmbito do diálogo internacional. As armas biológicas são tomadas como estudo de caso por sua relação intrínseca com a saúde e com a integridade de populações vulneráveis dos países periféricos

The study "Bioethics and biological weapons in an international context" investigates the application of an analysis from the perspective of intervention bioethics to international dialogues within a system of States. The case study tests the research method which consists in identifying and contrasting positions between developed and developing countries and their possibilities of their incorporation to rules, standards and regulations adopted by the international community. The analysis also considers the balance of opportunities between countries from the North and the South to insert their needs and interests in the rules of coexistence among States as indicative of the conditions of justice and equity in international dialogue. Biological weapons are taken as a case study for its intrinsic relationship with human health and the health of vulnerable populations of peripheral countries

Biological warfare agents.

Biological warfare agents are a group of pathogens and toxins of biological origin that can be potentially misused for military or criminal purposes. The present review attempts to summarize necessary knowledge about biological warfare agents. The historical aspects, examples of applications of these agents such as anthrax letters, biological weapons impact, a summary of biological warfare agents and epidemiology of infections are described. The last section tries to estimate future trends in research on biological warfare agents.

Dynamics of positional warfare malaria: Finland and Korea compared.

BACKGROUND: A sudden outbreak of vivax malaria among Finnish troops in SE-Finland and along the front line in Hanko peninsula in the southwest occurred in 1941 during World War II. The common explanation has been an invasion of infective Anopheles mosquitoes from the Russian troops crossing the front line between Finland and Soviet Union. A revised explanation is presented based on recent studies of Finnish malaria. METHODS: The exact start of the epidemic and the phenology of malaria cases among the Finnish soldiers were reanalyzed. The results were compared with the declining malaria in Finland. A comparison with a corresponding situation starting in the 1990's in Korea was performed. RESULTS AND DISCUSSION: The malaria cases occurred in July in 1941 when it was by far too early for infective mosquitoes to be present. The first Anopheles mosquitoes hatched at about the same time as the first malaria cases were observed among the Finnish soldiers. It takes about 3-6 weeks for the completion of the sporogony in Finland. The new explanation is that soldiers in war conditions were suddenly exposed to uninfected mosquitoes and those who still were carriers of hypnozoites developed relapses triggered by these mosquitoes. It is estimated that about 0.5% of the Finnish population still were carriers of hypnozoites in the 1940's. A corresponding outbreak of vivax malaria in Korea in the 1990's is similarly interpreted as relapses from activated hypnozoites among Korean soldiers. The significance of the mosquito induced relapses is emphasized by two benefits for the Plasmodium. There is a synchronous increase of gametocytes when new mosquitoes emerge. It also enables meiotic recombination between different strains of the Plasmodium. CONCLUSION: The malaria peak during the positional warfare in the 1940's was a short outbreak during the last phase of declining indigenous malaria in Finland. The activation of hypnozoites among a large number of soldiers and subsequent medication contributed to diminishing the reservoir of malaria and speeded up the eradication of the Finnish malaria. A corresponding evolution of Korean malaria is anticipated with relaxed tensions and decreasing troop concentrations along the border between South and North Korea.

O desenvolvimento biológico em conexão com a guerra / The Biological development in connection with the war

O século XX foi cenário da construção de um sistema para a operacionalização da ciência estratégica das grandes potências, chamada Big Science. Este sistema é constituído por uma vasta rede institucional integrada, o "complexo militar-industrial-acadêmico", que desenvolve pesquisas estratégicas e direciona a ciência de ponta. O objetivo deste estudo foi investigar a lógica desta construção sob a ótica do poder, fazendo um contraponto entre os desenvolvimentos tecnológicos da Física e da Biologia. Os movimentos de poder identificam algumas características que, em tese, refletem o incentivo para indução do desenvolvimento científico da modernidade, potencializado na era atômica com a fabricação de armas de destruição em massa, as armas de alta tecnologia. Nesta perspectiva, buscamos a relevância do desenvolvimento biológico de interesse político-militar, tomando por base a fabricação de três gerações de armas ao longo do século XX, com crescente posicionamento na corrida armamentista. Esta análise envolve as décadas de 1940 até 1980, na busca de demonstrar uma convergência técnico-política nas trajetórias do desenvolvimento biológico e da guerra biológica, que culminou numa conexão científico-militar no início da era biotecnológica.

The XX Century was the scenario for the construction of a system devoted to operationalizing the strategic science of the great potentials named the Big Science. This system comprehends a vast institutional and integrated network, the "military-industrial-academic complex", which carries out strategic research and guides high quality science. The objective of this study was to investigate the logics of such construction under the perspective of power, highlighting a counterpoint between the technological development of Physics and Biology. The power movement points to some characteristics, that theoretically reflect the incentive to the induction of the scientific development of modern times, potentialized during the atomic age by the manufacturing of high technology weapons. In this perspective one can search the relevance of the biological development of political-military interest in the three-generation manufacturing of weapons throughout the XX Century, and the participation in the armaments race. This historiographic analysis encompasses the decades of 1940 through 1980, in an attempt to show the ethnical-political convergence in the paths taken by the biological development and the biological war which eventually led to a scientific and military connection at the beginning of the biotechnological era.