Biowarfare, bioterrorism and biocrime: A historical overview on microbial harmful applications.

Microbial Forensics is a field that continues to grow in interest and application among the forensic community. This review, divided into two sections, covers several topics associated with this new field. The first section presents a historic overview concerning the use of microorganisms (or its product, i.e. toxins) as harmful biological agents in the context of biological warfare (biowarfare), bioterrorism, and biocrime. Each case is illustrated with the examination of case reports that span from prehistory to the present day. The second part of the manuscript is devoted to the role of MF and highlights the necessity to prepare for the pressing threat of the harmful use of biological agents as weapons. Preventative actions, developments within the field to ensure a timely and effective response and are discussed herein.

Pandemias, milicia e historia de la Ciencia / Pandemics, the military and the history of Science

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Angels and Devils: Dilemmas in Dual-Use Biotechnology.

Dual-use research, which results in knowledge that can be used for both good and ill, has become increasingly accessible in the internet age to both scientists and the general public. Here, we outline some major milestones for dual-use policy and present three vignettes that highlight contemporary dual-use issues in biotechnology.

Unit 731 and moral repair.

Unit 731, a biological warfare research organisation that operated under the authority of the Imperial Japanese Army in the 1930s and 1940s, conducted brutal experiments on thousands of unconsenting subjects. Because of the US interest in the data from these experiments, the perpetrators were not prosecuted and the atrocities are still relatively undiscussed. What counts as meaningful moral repair in this case-what should perpetrators and collaborator communities do decades later? We argue for three non-ideal but realistic forms of moral repair: (1) a national policy in Japan against human experimentation without appropriate informed and voluntary consent; (2) the establishment of a memorial to the victims of Unit 731; and (3) US disclosure about its use of Unit 731 data and an apology for failing to hold the perpetrators accountable.

Open-Air Biowarfare Testing and the Evolution of Values.

The United States and the United Kingdom ended outdoor biological warfare testing in populated areas nearly half a century ago. Yet, the conduct, health effects, and propriety of those tests remain controversial. The varied views reflect the limits of currently available test information and evolving societal values on research involving human subjects. Western political culture has changed since the early days of the American and British testing programs. People have become less reluctant to question authority, and institutional review boards must now pre-approve research involving human subjects. Further, the heightened stringency of laboratory containment has accentuated the safety gap between a confined test space and one without physical boundaries. All this makes it less likely that masses of people would again be unwittingly subjected to secret open-air biological warfare tests.

Neurotoxic Weapons and Syndromes.

The modern era of chemical and biological warfare began in World War I with the large-scale production and use of blistering and choking agents (chlorine, phosgene and mustard gases) in the battlefield. International treaties (the 1925 Geneva Protocol, the 1975 Biological and Toxin Weapons Convention and the 1993 Chemical Weapons Convention) banned biological and chemical weapons. However, several countries are probably still engaged in their development. Hence, there is risk of these weapons being used in the future. This chapter will focus on neurotoxic weapons (e.g. nerve agents, chemical and biological neurotoxins, psychostimulants), which act specifically or preeminently on the central nervous system and/or the neuromuscular junction. Deeply affecting the function of the nervous system, these agents either have incapacitating effects or cause clusters of casualties who manifest primary symptoms of encephalopathy, seizures, muscle paralysis and respiratory failure. The neurologist should be prepared both to notice patterns of symptoms and signs that are sufficiently consistent to raise the alarm of neurotoxic attacks and to define specific therapeutic interventions. Additionally, extensive knowledge on neurotoxic syndromes should stimulate scientific research to produce more effective antidotes and antibodies (which are still lacking for most neurotoxic weapons) for rapid administration in aerosolized forms in the case of terrorist or warfare scenarios.

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.

Biological Warfare Plan in the 17th Century­the Siege of Candia, 1648­1669.

A little-known effort to conduct biological warfare occurred during the 17th century. The incident transpired during the Venetian­Ottoman War, when the city of Candia (now Heraklion, Greece) was under siege by the Ottomans (1648­1669). The data we describe, obtained from the Archives of the Venetian State, are related to an operation organized by the Venetian Intelligence Services, which aimed at lifting the siege by infecting the Ottoman soldiers with plague by attacking them with a liquid made from the spleens and buboes of plague victims. Although the plan was perfectly organized, and the deadly mixture was ready to use, the attack was ultimately never carried out. The conception and the detailed cynical planning of the attack on Candia illustrate a dangerous way of thinking about the use of biological weapons and the absence of reservations when potential users, within their religious framework, cast their enemies as undeserving of humanitarian consideration.

History of biological warfare and bioterrorism.

Bioterrorism literally means using microorganisms or infected samples to cause terror and panic in populations. Bioterrorism had already started 14 centuries before Christ, when the Hittites sent infected rams to their enemies. However, apart from some rare well-documented events, it is often very difficult for historians and microbiologists to differentiate natural epidemics from alleged biological attacks, because: (i) little information is available for times before the advent of modern microbiology; (ii) truth may be manipulated for political reasons, especially for a hot topic such as a biological attack; and (iii) the passage of time may also have distorted the reality of the past. Nevertheless, we have tried to provide to clinical microbiologists an overview of some likely biological warfare that occurred before the 18th century and that included the intentional spread of epidemic diseases such as tularaemia, plague, malaria, smallpox, yellow fever, and leprosy. We also summarize the main events that occurred during the modern microbiology era, from World War I to the recent 'anthrax letters' that followed the World Trade Center attack of September 2001. Again, the political polemic surrounding the use of infectious agents as a weapon may distort the truth. This is nicely exemplified by the Sverdlovsk accident, which was initially attributed by the authorities to a natural foodborne outbreak, and was officially recognized as having a military cause only 13 years later.

Biological warfare warriors, secrecy and pure science in the Cold War: how to understand dialogue and the classifications of science.

This paper uses a case study from the Cold War to reflect on the meaning at the time of the term 'Pure Science'. In 1961, four senior scientists from Britain's biological warfare centre at Porton Down visited Moscow both attending an International Congress and visiting Russian microbiological and biochemical laboratories. The reports of the British scientists in talking about a limited range of topics encountered in the Soviet Union expressed qualities of openness, sociologists of the time associated with pure science. The paper reflects on the discourses of "Pure Science", secrecy and security in the Cold War. Using Bakhtin's approach, I suggest the cordial communication between scientists from opposing sides can be seen in terms of the performance, or speaking, of one language among several at their disposal. Pure science was the language they were allowed to share outside their institutions, and indeed political blocs.

[The re-introduction of malaria in the Pontine Marshes and the Cassino district during the end of World War II. Biological warfare or global war tactics?]. / La reintroduzione della malaria nell'Agro Pontino e a Cassino sul finire della II Guerra Mondiale. Guerra biologica o tattica di guerra totale?

After the fall of the Fascist regime on September 8, 1943, Italy was split into two parts: (i) the Southern regions where the King Victor Emanuel III and the military general staff escaped was under the control of English-American allied armies, and (ii) the northern regions comprising Lazio, Tuscany, Umbria, and Marche still under the control of the Germans. The German Wehrmacht, after suffering several defeats on Southern lines, established a new strengthened line of defence called the Gustav line, located south of Rome and crossing in the western portion the recently-drained Pontine Marshes. In his book published in 2006, Frank Snowden hypothesised that occupying German armies in 1943 had initiated a programme of re-flooding the Pontine plain as a biological warfare strategy to re-introduce malaria infection in the territories south of Rome, Such a plan was intended (i) to slow down the advance of English-American forces, and (ii) to punish Italians who abandoned their former allies. Other authors, including Annibale Folchi, Erhard Geissler, and Jeanne Guillemin, have disputed this hypothesis based on an analysis of recently-uncovered archive documents. What is not disputed is that the flooding of the Pontine and Roman plains in 1943 contributed to a severe malaria epidemic in 1944, which was associated with exceptionally high morbidity and mortality rates in the afflicted populations. Herein, we critically evaluate the evidence and arguments of whether the Wehrmacht specifically aimed to spread malaria as a novel biological warfare strategy in Italy during the Second World War. In our opinion, evidence for specific orders to deliberately spread malaria by the German army is lacking, although the strategy itself may have been considered by Nazis during the waning years of the war.

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.

German flooding of the Pontine Marshes in World War II.

The German army's 1943 flooding of the Pontine Marshes south of Rome, which later caused a sharp rise in malaria cases among Italian civilians, has recently been described by historian Frank Snowden as a unique instance of biological warfare and bioterrorism in the European theater of war and, consequently, as a violation of the 1925 Geneva Protocol prohibiting chemical and biological warfare. We argue that archival documents fail to support this allegation, on several counts. As a matter of historical record, Hitler prohibited German biological weapons (BW) development and consistently adhered to the Geneva Protocol. Rather than biological warfare against civilians, the Wehrmacht used flooding, land mines, and the destruction of vital infrastructure to obstruct the Allied advance. To protect its own troops in the area, the German army sought to contain the increased mosquito breeding likely to be caused by the flooding. Italians returning to the Pontine Marshes after the German retreat in 1944 suffered malaria as a result of environmental destruction, which was banned by the 1899 and 1907 Hague Conventions and by subsequent treaties. In contrast, a state's violation of the Geneva Protocol, whether past or present, involves the use of germ weapons and, by inference, a state-level capability. Any allegation of such a serious violation demands credible evidence that meets high scientific and legal standards of proof.

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.

Military medicine and the ethics of war: British colonial warfare during the Seven Years War (1756-63).

This article examines 18th-century European warfare, tracing the first formal codifications of conventions of war, frequently introduced by military physicians and initially regarding the treatment of the sick and wounded. It outlines to what extent these conventions were followed in practice, particularly in the challenging environment of American irregular warfare, with a focus on the most well-known incident of "biological warfare" in the period: the deliberate spread of smallpox by British officers among Amerindians in 1763. More broadly, it demonstrates that the history of military medicine provides a fruitful method with which to uncover assumptions about the ethics of war.

[The American bacteriologist: Dr. Meyer].

Karl F. Meyer who was born in Switzerland was American famous bacteriologist of 20th century. During the World War II, Dr. Meyer urged the U. S. military to take positive reply measures against the bacteria war started by Japanese army and achieved significant accomplishments in the preventive and therapeutic theory of plague as well as the manufacture of plague vaccine. After the World War II, Meyer devoted to the scientific field of plague prevention and made great achievements in the area of animal diseases and public health. In 1951, he received the Lasker Award of America.

Is all fair in biological warfare? The controversy over genetically engineered biological weapons.

Advances in genetics may soon make possible the development of ethnic bioweapons that target specific ethnic or racial groups based upon genetic markers. While occasional published reports of such research generate public outrage, little has been written about the ethical distinction (if any) between the development of such weapons and ethnically neutral bioweapons. The purpose of this paper is to launch a debate on the subject of ethnic bioweapons before they become a scientific reality.

[An epidemic of typhoid fever among the German troops in Paris, Christmas 1941]. / Une epidémie de fièvre typhoïde parmi les troupes allemandes a Paris a Noël 1941.

In 1941, at Christmastime more than 600 German soldiers visited Paris and were infected with the bacillus of Eberth, the agent of typhoid fever. All of the infections occurred at the Brasserie La Brune situated in the center of Paris. It was, in fact, an act of Resistance. The proof of the infection was rapidly given by Lucien Brumpt using a home-made hemodiagnostic method. This quick hemodiagnostic technique is easy to perform, inexpensive and still could be used.

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.