Biologics, A History Of Agents Made From Living...
The Caffa incident was described in 1348 or 1349 by Gabriel de Mussis, a notary born in Piacenza north of Genoa (6). De Mussis made two important claims: plague was transmitted to the citizens of Caffa by the hurling of diseased cadavers into the besieged city, and Italians fleeing from Caffa brought the plague into the Mediterranean seaports (4). In fact, ships carrying plague-infected refugees (and possibly rats) sailed to Constantinople, Genoa, Venice, and other Mediterranean seaports and are thought to have contributed to the second plague pandemic. However, given the complex ecology and epidemiology of plague, it may be an oversimplification to assume that a single biological attack was the sole cause of the plague epidemic in Caffa and even the 14th-century plague pandemic in Europe (3). Nonetheless, the account of a biological warfare attack in Caffa is plausible and consistent with the technology of that time, and despite its historical unimportance, the siege of Caffa is a powerful reminder of the terrible consequences when diseases are used as weapons.
Biologics, A History of Agents Made From Living...
In addition to these efforts in the USA, many other countries continued their biological weapons research, including Canada, Britain, France, and the Soviet Union. In the United Kingdom, the Microbiological Research Department was established in 1947 and expanded in 1951 (2, 21). Plans for pilot biological warfare were made, and research continued on the development of new biological agents and weapons design. Britain conducted several trials with biological warfare agents in the Bahamas, in the Isles of Lewis, and in Scottish waters to refine these weapons. However, in 1957, the British government decided to abandon the offensive biological warfare research and to destroy stockpiles. At that time, a new emphasis was put on further development of biological defensive research (21). At the same time, the Soviet Union increased its efforts in both offensive and defensive biological warfare research and development (1). Reports regarding offensive research repeatedly occurred in the 1960s and 1970s, although officially the Soviet Union claimed not to possess any biological or chemical weapons.
Two weeks later, after he had learned of Markov's death, Kostov was examined by French doctors. They removed a similar pellet, which was made from an exotic alloy of iridium and platinum and contained the toxin ricin.
While biologics, such as antibodies, target cancer cells for destruction, others serve as supportive care and can work to reduce the side effects from chemotherapy or radiation treatments. One class of biologics, known as colony-stimulating factors (CSFs), encourage bone marrow to grow and divide. Additionally, CSFs can increase the number of infection-fighting white blood cells in the body and help patients receiving chemotherapy tolerate their treatments at higher more effective doses.
Biologics include medicines that generally come from living organisms, which can include animal cells and microorganisms, such as yeast and bacteria. That makes biologics different from conventional medications, which are commonly made from chemicals.
Historically, outbreaks (wars) of microbial species against the human species have killed far more people than war itself. Examples include i) killing of 95% of Pre-Columbian Native American populations by diseases like small pox, measles, plague, typhoid and influenza; ii) death of 25 million Europeans (a quarter of the population) caused by Bubonic Plague in the 14th century and 21 million deaths due to the influenza pandemic of 1918-1919 (1).Worldwide, naturally occurring infectious diseases remain the major causes of death. In the United States, the impact of a number of very virulent biological agents and/or their toxins has been drastically reduced because of a very accessible health care system and excellent public health infrastructure. Still, a substantial number of people (approximately 70,000) die each year from infectious diseases (2). The travel and trade necessary for economic globalization, continued potential for transmission of infectious agents from animals to humans, and large populations living in proximity in major urban areas of the world, make disease outbreaks a major threat. The resistance of common pathogens to the available antimicrobial agents adds significantly to the threat. Advances in public health, diagnostic and pharmacological interventions are needed to protect the population from emerging and re-emerging infectious diseases. The global nature of infectious disease threats is well described in a statement prepared by Dr. David L. Heymann, Executive Director for Communicable Diseases, World Health Organization. This statement was presented to the Committee on Foreign Relations, United States Senate, during a hearing on "The Threat of Bioterrorism and the Spread of Infectious Diseases" on September 5, 2001 (3).
A critique of the Model State Emergency Health Powers Act was published by Annas G. In Bioterrorism, Public Health and Civil Liberties. NEJM, 2002 April 24:346(13) At the federal level, Public Health Security and Bioterrorism Preparedness and Response Act of 2002, HR 3448, was passed by the United States Congress on May 23, 2002 and signed into law (Public Law 107-188) June 12, 2002. The bill is intended to improve the health system's ability to respond to bioterrorism, protect the nation's food supply and drinking water from bioterrorist attacks, speed the development and production of new drug treatments and vaccines, address shortages of specific types of health professions, improve coordination of federal anti-bioterrorism activities, increase investment in federal, state, and local preparedness and expand controls over the most dangerous biological agents and toxins. The American Society for Microbiology (ASM) has testified before congress on issues surrounding biosecurity and has worked closely with congress in the drafting of Title II to balance Public Health concern over safely and security with need to protect legitimate scientific research and diagnostic testing. Important new provisions for the possession, use and transfer of select agents, (42 biological agents and toxins listed in Appendix A of 42 CFR part 72), are included in Title II of HR 3448, Enhancing Controls on Dangerous Biological Agents and Toxins. On July 12, 2002, the CDC announced preliminary guidance for notification of possession of select agents as mandated in Section 202 (a) of Public Law 107-188, the Public Health Security and Bioterrorism Preparedness and Response Act of 2002 (Appendix B). The notice states that each facility should designate a responsible facility official (RFO) to complete the notification of possession form by September 10, 2002. The RFO will need to inventory the facility and consult with others (e.g. Principal Investigators) to obtain the required information. At our institution a Designated Safety Officer in collaboration with the Infection Control and Safety Committee address these issues. In order to avoid inconsistencies and noncompliance, at the July meeting, it was recommended to the Committee that the Principal Investigators provide a complete list of all the biological agents being used in their laboratories. The Safety Officer would then use the information needed to register with the Secretary of Health and Human Services and provide inspections to ensure safety and compliance with the requirements.
The origin of the biological weapons program of the former Soviet Union dates back to statements by Lenin. Although experimental work was started in the late 1920's, the modern era was ushered in only with the postwar military building programs (22). The Allied Biological Weapons program had shifted from the British research into anthrax (and the development of the World War II anthrax cattlecake retaliation weapon), to a large United States based research, development and production capability. The United States military had accepted seven types of classified agents and could produce 650 tons of an agent per month at plants such as the one at Pine Bluff in Arkansas. This offensive program was unilaterally abandoned in 1969, giving impetus to the creation of the Biological and Toxin Weapons Convention. The Soviet Union signed the Convention at its inception in 1972. Unfortunately, the number of countries engaged in biological weapons experimentation has grown from 4 in the 1960's to 11 in the 1990's (23). It is estimated that at least 10 nations and possibly 17 possess biological warfare agents (24) . Of the seven countries listed by the United States Department of State as sponsoring international terrorism, at least five are suspected to have biological warfare programs (25). Nations and dissident groups have the access to skills needed to selectively cultivate some of the most dangerous pathogens and to deploy them as agents of biological terrorism and war (26).
The Biological weapons system is comprised of four components; a payload, munition, delivery system and dispersion system. The payload is the biological agent itself. The munition protects and carries the payload to maintain its potency during delivery. The delivery system can be a missile, vehicle (aircraft, boat, automobile or truck), or an artillery shell. The dispersion system ensures dissemination of the payload at the target site. Potential methods of dispersion are aerosol sprays, explosives, and food or water contamination. Aerosol sprays are the most effective means of widespread dissemination. Depending on atmospheric conditions and the agent itself, infectious material could travel several hundred kilometers in a particle size that upon inhalation would be delivered to the terminal airways. However factors like particle size of the agent, stability of the agent under desiccating conditions and ultraviolet light, wind speed, wind direction, and atmospheric stability can alter the effectiveness of a given delivery system. Explosions are likely to inactivate biological agents and therefore are not very effective in disseminating infectious materials. Contamination of water supplies generally requires an addition of an unrealistically large amount of biological agent(s) to a city supply. The agents may be introduced into smaller reservoirs or into the water supply after the water passes through its purification facility. Food supplies are easier to contaminate than water supplies. The outbreaks from food source may be dismissed as a "natural" event early during a bioterrorism attack (30, 31). 041b061a72