The Threat of Bioweapons

Immediately following 9-11, an anthrax attack originating from letters containing anthrax spores infected 22 people, killing five.  After almost six years, the case has not been solved. 

Intelligence analysts and academics report that North Korea has developed anthrax, plague, and botulism toxin and conducted extensive research on smallpox, typhoid and cholera. 

A world-renowned bioweapons expert has confirmed that Syria has weapons grade smallpox resistant to all current vaccines developed under the cover of legitimate veterinary research  on camelpox, a very closely related virus.  The researcher further reports that Syria is suspected of testing the pathogen on prison populations and possibly in the Sudan. 

Although there are close to 50 organisms that could be used offensively, rogue nations have concentrated their bioweapons development efforts on smallpox, anthrax, plague, botulinum, tularemia and viral hemorrhagic fevers.  With the exception of smallpox, which is exclusively a human host disease, all of the other pathogens lend themselves to animal testing as they are zoonotic, or can be transmitted to humans by other species. 

Biological weapons are among the most dangerous in the world today and can be engineered and disseminated to achieve a more deadly result than a nuclear attack.  Whereas the explosion of a nuclear bomb would cause massive death in a specific location, a biological attack with smallpox could infect multitudes of people across the globe.  With incubation periods of up to 17 days, human disseminators could unwittingly cause widespread exposure before diagnosable symptoms indicate an infection and appropriate quarantine procedures are in place. 

Unlike any other type of weapon, bioweapons such as smallpox can replicate and infect a chain of people over an indeterminate amount of time from a single undetectable point of release.  According to science writer and author of The Hot Zone, Richard Preston, "If you took a gram of smallpox, which is highly contagious and lethal, and for which there's no vaccine available globally now, and released it in the air and created about a hundred cases, the chances are excellent that the virus would go global in six weeks as people moved from city to city......the death toll could easily hit the hundreds of millions.....in scale, that's like a nuclear war."[1]   

More so than chemical and nuclear research, bioweapons development programs lend themselves to stealth development.  They are difficult to detect, can be conducted alongside legimate research on countermeasures, sheltered in animal research facilities within sophisticated pharmaceutical corporations, disguised as part of routine medical university studies, or be a component of dual use technology development.  Detection is primarily through available intelligence information and location-specific biosensors that test for the presence of pathogens.

Biological weapons have many appealing qualities for warfare and their effects can be engineered and customized from a boutique of possibilities.  Offensive pathogens are inexpensive compared to conventional weapons and small quantities can produce disproportionate damage.  They have unlimited lethal potential as carriers and can continue to infect more people over time.  Bioweapons are easy to dispense through a variety of delivery systems from a missile, an aerosol or a food product.  They can be placed into a state of dormancy to be activated at a later stage allowing for ease of storage.  Pathogens are not immediately detectable or identifiable due to varying incubation periods and can be rapidly deployed, activated and impossible to trace.  The technology to develop biological agents is widely available for legitimate purposes and large quantities can be developed within days. 

Bioweapons can be tailored for specific situations from a variety of desired characteristics, including pathogenicity or disease-producing capacity, incubation period, virulence and transmissibility.  Pathogenicity is relative to the quantity of a particular agent that is necessary to cause disease.  The incubation period is critical for determining the timing of the desired period between exposure and the onset of illness.  Virulence determines how debilitating and lethal the disease will manifest in the target population.  Transmissibility defines the ease in which the disease is able to spread. 

The ultimate goal of bioterrorism is to induce fear, panic and chaos by high morbidity and mortality rates to breakdown the existing political, economic and social structure.  For bioweapons to be successful, "The biological agent should consistently produce the desire effect of death or disease.  It should be highly contagious with short and predictable incubation period and infective in low doses.  The disease should be difficult to identify and be suspected as an act of bioterrorism.  The agents should be suitable for mass production, storage, weaponization, and stable during dissemination.  The target population should have little or no herd immunity and little or no access to treatment.  The terrorist should have means to protect or treat their own forces and population against the infectious agents or the toxins."[2]

Due to their virulence, ease of dissemination and detection difficulties, bioweapons experts and the Department of Homeland Security assert that smallpox and anthrax are the most worrisome biothreats to national security.  Both have been weaponized which means they can be produced in a particle size that is releasable in the air and can be easily inhaled into the respiratory system.  Both smallpox and anthrax are extremely deadly and present unique forensic, environmental, logistical and public health care delivery challenges.

Smallpox

Although smallpox was officially eradicated in 1980, there is evidence of the virus beyond the two World Health Organization-designated repositories.  There is little immunity in the U.S. population as the smallpox vaccination program ended in 1963 and the vaccinations are believed to be effective for a ten year period. 

Following 9-11 and heightened fears of a bioattack, the U.S. government, under the direction of Health and Human Services, revitalized the smallpox program and by 2003 acquired sufficient live-virus vaccines in the Strategic National Stockpile for the entire population.  Approximately 50-60 million Americans are identified either as high risk for developing post-vaccination complications or unable to be vaccinated.  These include individuals who are allergic to vaccine components, are HIV-positive, have immune system disorders, are undergoing chemotherapy, have certain dermatologic conditions and pregnant and breast-feeding women.  

The FDA just recommended for approval a new smallpox vaccine that is grown in a cell culture in a laboratory and has less of a risk of complications.  It can be used for populations who can't receive the conventional smallpox vaccination and will most likely be added to the stockpile within the next year.  An anti-viral drug that effectively treats adverse vaccine reactions will be purchased for the stockpile as well. 

The challenges presented by a smallpox outbreak are numerous for diagnosis, surveillance and containment.  Although easily diagnosed, the majority of practicing physicians has never seen a case of smallpox and may not accurately identify symptoms at first.  Due to the long incubation period, infected individuals may remain undetected for extended periods leading to misjudgments in the trajectory of the epidemic and delayed implementation of quarantine procedures.  Potential contacts of cases may be too great to effectively trace and monitor.  Also, the vaccine is ineffective beyond the first few days of exposure when people are asymptomatic and few health care workers have been immunized.  During the 20th century, with greater immunity, smallpox killed 300 million people.

Anthrax

Anthrax is a serious disease that is caused by spore-producing bacteria that releases toxins in the body.  It cannot be spread through direct human contact but can be transported on inanimate objects and disseminated through the air.  Anthrax infections can occur through the skin, by inhalation and by ingesting contaminated food. 

Anthrax presents difficult challenges for clean-up and decontamination.  The spores tend to be widely dispersed in the environment and can survive for long periods of time after release.  Decontamination procedures are costly and extremely time-consuming as the bacteria is highly stable and maintains its potency.

A number of treatments exist for anthrax infections and several are in the national stockpile or in the process of being acquired.  Vaccinations provide pre-exposure protection for individuals at high risk for anthrax contact. For post-exposure, a combination of vaccination and oral antibiotics is used.  For those who are symptomatic, intravenous antibiotics are the treatment of choice.  HHS is in the process of acquiring the next generation of anthrax vaccine that can be produced more rapidly than what is currently available. Also, drugs that clean up the toxins excreted by anthrax bacteria are being developed and will be added to the stockpile. 

September 11th and the anthrax attack that followed were watershed events that spawned programs to fight bioterrorism.  The newly established DHS was charged with the responsibility of performing threat assessments and communicating the need for countermeasures to Health and Human Services to procure countermeasures for the national stockpile.  In 2002, several programs were enacted by the Bush administration to create the necessary infrastructure for the detection and necessary interventions for a bioterrorist attack against the United States.  The programs include Project BioWatch, Project BioSense and Project BioShield.    

Project BioWatch

Project BioWatch is an early biothreat detection system coordinated through the Department of Homeland Security (DHS), the Environmental Protection Agency (EPA) and the Center for Disease Control (CDC) with the goal of minimizing casualties, assisting law enforcement efforts and identifying exposed populations and contamination patterns. BioWatch monitors a network of biosensors or filters in 30 U.S. cities that detect the presence of biological materials, capture samples and analyze them in a field laboratory.  The current system tests for the existence of up to eight toxins, bacteria and viruses.  If bioagents are detected, BioWatch has a series of protocols to follow to initiate an appropriate course of action and affect public health policy.  The acquisition and implementation of next generation technology biosensors that will perform insitu sample collection, analysis and wirelessly report biothreats is being explored by DHS and should be ready for pilot testing shortly.  The new technology, which can test for around 20 pathogens, will provide cost savings that could possibly result in greater coverage or increased density within currently monitored locations.  

Project Biosense

Project BioSense was established to reduce the time between the detection of a potential biothreat and the initiation of an appropriate response.  It's primary function is to analyze multiple data streams from hospitals, pharmacies, Project BioWatch and other relevant sources, for the purpose of expediting a coordinated comprehensive response.  The goal is to have a single center collect and evaluate available data and transmit critical threat information to health care providers.  It aims to strengthens the working relationship between the CDC and the caregivers on the frontlines in a biothreat emergency.

Project Bioshield

Project Bioshield's charter is to procure vaccinations and drugs for potential biothreats for the national stockpile.  In 2004, $5.6 billion was allocated over ten years to fund research and purchase countermeasures against threats from private companies.  Bioshield was established to simplify the procurement process and enable the FDA and the NIH to partner with research communities and the biopharma industry in the fight against bioterrorism.  In its initial stages, it was difficult for Project Bioshield to incentivize biotechnology companies to develop countermeasures for bioweapons.  More lucrative drug development projects for cancer and HIV had greater market potential and promised better returns on investment.  Also, Project Bioshield contracts included extensive regulations, offered no liability protection, and lacked purchase guarantees. Private companies were incurring all of the risk of doing business with the government and received no payments until the actual delivery of products to the stockpile.  Once a product was developed, companies were saddled with costs for extensive testing that could span a five year period and be difficult to recover.     

In 2005, BARDA, the Biomedical Advanced Research and Development Authority, was established to facilitate the development of medical countermeasures against national security threats.  BARDA simplified the procurement process, provided liability protection for private companies and advanced development money for testing promising products.   

Two new bills have been proposed to improve the national response to biological threats.  The Material Threats Act, H.R. 1089, aims to improve the ability of DHS to assess chemical, biological, radiological and nuclear threats and the availability and effectiveness of countermeasures that may be grouped together to address multiple threats.  The second bill, H.R. 1290, establishes a National Biosurveillance Integration Center to monitor, review and consolidate data from multiple sources in the event of a biological incident.

Conclusion

The testimony before Congress in April of 2006 of Tara O'Toole, M.D., M.P.H., Director and CEO of the Center for Biosecurity at the University of Pittsburgh Medical Center sums up the current situation vis a vis biothreats.  "The U.S. does not yet have a coherent biodefense strategy, nor do we have a strategy for countermeasure research, development, and production that takes account of the full spectrum of possible bioweapons agents, including engineered threats."[3]  Dr. O'Toole went on to explain the urgency for national security of developing and stockpiling countermeasures against high-priority threats such as anthrax, smallpox, plague and others.  In the long term, she criticized the futility of chasing countermeasures for specific pathogens due to the multitude of pathogens that are potentially weaponizable.  What is needed according to Dr. O'Toole is the "ability to rapidly design, develop and produce new countermeasures from a standing start - in weeks, if not days."[4]  This will occur with technological improvements, wider sharing and accessibility of data, streamlined clinical testing and regulatory review and through public-private partnerships.

Even with the BioWatch, BioSense and BioShield projects, still in their infancy, current measures fall far short of this broad, well thought out approach. The two proposed Congressional bills are a step forward. But the United States remains almost as ill prepared today to cope with a bioweapons attack as it proved itself to be shortly after 9/11. We must begin to remedy this now.

[1] "A conversation with Richard Preston" in Laboratory Medicine, vol. 30, pg 517 Aug. 1999.

[2] Beeching NJ, Dance DA, Miller AR, et. al. Biological warfare and bioterrorism.  BMJ 2002; 324:336-339. 

[3] Tara O'Toole, MD, MPH, Hearing on "Project BioShield Reauthorization Issues," testimony before the Congress of the United States, April 6, 2006.

http://upmc-biosecurity.org/website/resources/hearings/content/Hearings_2006/20060406bioshldreauth.html

[4] ibid.
Immediately following 9-11, an anthrax attack originating from letters containing anthrax spores infected 22 people, killing five.  After almost six years, the case has not been solved. 

Intelligence analysts and academics report that North Korea has developed anthrax, plague, and botulism toxin and conducted extensive research on smallpox, typhoid and cholera. 

A world-renowned bioweapons expert has confirmed that Syria has weapons grade smallpox resistant to all current vaccines developed under the cover of legitimate veterinary research  on camelpox, a very closely related virus.  The researcher further reports that Syria is suspected of testing the pathogen on prison populations and possibly in the Sudan. 

Although there are close to 50 organisms that could be used offensively, rogue nations have concentrated their bioweapons development efforts on smallpox, anthrax, plague, botulinum, tularemia and viral hemorrhagic fevers.  With the exception of smallpox, which is exclusively a human host disease, all of the other pathogens lend themselves to animal testing as they are zoonotic, or can be transmitted to humans by other species. 

Biological weapons are among the most dangerous in the world today and can be engineered and disseminated to achieve a more deadly result than a nuclear attack.  Whereas the explosion of a nuclear bomb would cause massive death in a specific location, a biological attack with smallpox could infect multitudes of people across the globe.  With incubation periods of up to 17 days, human disseminators could unwittingly cause widespread exposure before diagnosable symptoms indicate an infection and appropriate quarantine procedures are in place. 

Unlike any other type of weapon, bioweapons such as smallpox can replicate and infect a chain of people over an indeterminate amount of time from a single undetectable point of release.  According to science writer and author of The Hot Zone, Richard Preston, "If you took a gram of smallpox, which is highly contagious and lethal, and for which there's no vaccine available globally now, and released it in the air and created about a hundred cases, the chances are excellent that the virus would go global in six weeks as people moved from city to city......the death toll could easily hit the hundreds of millions.....in scale, that's like a nuclear war."[1]   

More so than chemical and nuclear research, bioweapons development programs lend themselves to stealth development.  They are difficult to detect, can be conducted alongside legimate research on countermeasures, sheltered in animal research facilities within sophisticated pharmaceutical corporations, disguised as part of routine medical university studies, or be a component of dual use technology development.  Detection is primarily through available intelligence information and location-specific biosensors that test for the presence of pathogens.

Biological weapons have many appealing qualities for warfare and their effects can be engineered and customized from a boutique of possibilities.  Offensive pathogens are inexpensive compared to conventional weapons and small quantities can produce disproportionate damage.  They have unlimited lethal potential as carriers and can continue to infect more people over time.  Bioweapons are easy to dispense through a variety of delivery systems from a missile, an aerosol or a food product.  They can be placed into a state of dormancy to be activated at a later stage allowing for ease of storage.  Pathogens are not immediately detectable or identifiable due to varying incubation periods and can be rapidly deployed, activated and impossible to trace.  The technology to develop biological agents is widely available for legitimate purposes and large quantities can be developed within days. 

Bioweapons can be tailored for specific situations from a variety of desired characteristics, including pathogenicity or disease-producing capacity, incubation period, virulence and transmissibility.  Pathogenicity is relative to the quantity of a particular agent that is necessary to cause disease.  The incubation period is critical for determining the timing of the desired period between exposure and the onset of illness.  Virulence determines how debilitating and lethal the disease will manifest in the target population.  Transmissibility defines the ease in which the disease is able to spread. 

The ultimate goal of bioterrorism is to induce fear, panic and chaos by high morbidity and mortality rates to breakdown the existing political, economic and social structure.  For bioweapons to be successful, "The biological agent should consistently produce the desire effect of death or disease.  It should be highly contagious with short and predictable incubation period and infective in low doses.  The disease should be difficult to identify and be suspected as an act of bioterrorism.  The agents should be suitable for mass production, storage, weaponization, and stable during dissemination.  The target population should have little or no herd immunity and little or no access to treatment.  The terrorist should have means to protect or treat their own forces and population against the infectious agents or the toxins."[2]

Due to their virulence, ease of dissemination and detection difficulties, bioweapons experts and the Department of Homeland Security assert that smallpox and anthrax are the most worrisome biothreats to national security.  Both have been weaponized which means they can be produced in a particle size that is releasable in the air and can be easily inhaled into the respiratory system.  Both smallpox and anthrax are extremely deadly and present unique forensic, environmental, logistical and public health care delivery challenges.

Smallpox

Although smallpox was officially eradicated in 1980, there is evidence of the virus beyond the two World Health Organization-designated repositories.  There is little immunity in the U.S. population as the smallpox vaccination program ended in 1963 and the vaccinations are believed to be effective for a ten year period. 

Following 9-11 and heightened fears of a bioattack, the U.S. government, under the direction of Health and Human Services, revitalized the smallpox program and by 2003 acquired sufficient live-virus vaccines in the Strategic National Stockpile for the entire population.  Approximately 50-60 million Americans are identified either as high risk for developing post-vaccination complications or unable to be vaccinated.  These include individuals who are allergic to vaccine components, are HIV-positive, have immune system disorders, are undergoing chemotherapy, have certain dermatologic conditions and pregnant and breast-feeding women.  

The FDA just recommended for approval a new smallpox vaccine that is grown in a cell culture in a laboratory and has less of a risk of complications.  It can be used for populations who can't receive the conventional smallpox vaccination and will most likely be added to the stockpile within the next year.  An anti-viral drug that effectively treats adverse vaccine reactions will be purchased for the stockpile as well. 

The challenges presented by a smallpox outbreak are numerous for diagnosis, surveillance and containment.  Although easily diagnosed, the majority of practicing physicians has never seen a case of smallpox and may not accurately identify symptoms at first.  Due to the long incubation period, infected individuals may remain undetected for extended periods leading to misjudgments in the trajectory of the epidemic and delayed implementation of quarantine procedures.  Potential contacts of cases may be too great to effectively trace and monitor.  Also, the vaccine is ineffective beyond the first few days of exposure when people are asymptomatic and few health care workers have been immunized.  During the 20th century, with greater immunity, smallpox killed 300 million people.

Anthrax

Anthrax is a serious disease that is caused by spore-producing bacteria that releases toxins in the body.  It cannot be spread through direct human contact but can be transported on inanimate objects and disseminated through the air.  Anthrax infections can occur through the skin, by inhalation and by ingesting contaminated food. 

Anthrax presents difficult challenges for clean-up and decontamination.  The spores tend to be widely dispersed in the environment and can survive for long periods of time after release.  Decontamination procedures are costly and extremely time-consuming as the bacteria is highly stable and maintains its potency.

A number of treatments exist for anthrax infections and several are in the national stockpile or in the process of being acquired.  Vaccinations provide pre-exposure protection for individuals at high risk for anthrax contact. For post-exposure, a combination of vaccination and oral antibiotics is used.  For those who are symptomatic, intravenous antibiotics are the treatment of choice.  HHS is in the process of acquiring the next generation of anthrax vaccine that can be produced more rapidly than what is currently available. Also, drugs that clean up the toxins excreted by anthrax bacteria are being developed and will be added to the stockpile. 

September 11th and the anthrax attack that followed were watershed events that spawned programs to fight bioterrorism.  The newly established DHS was charged with the responsibility of performing threat assessments and communicating the need for countermeasures to Health and Human Services to procure countermeasures for the national stockpile.  In 2002, several programs were enacted by the Bush administration to create the necessary infrastructure for the detection and necessary interventions for a bioterrorist attack against the United States.  The programs include Project BioWatch, Project BioSense and Project BioShield.    

Project BioWatch

Project BioWatch is an early biothreat detection system coordinated through the Department of Homeland Security (DHS), the Environmental Protection Agency (EPA) and the Center for Disease Control (CDC) with the goal of minimizing casualties, assisting law enforcement efforts and identifying exposed populations and contamination patterns. BioWatch monitors a network of biosensors or filters in 30 U.S. cities that detect the presence of biological materials, capture samples and analyze them in a field laboratory.  The current system tests for the existence of up to eight toxins, bacteria and viruses.  If bioagents are detected, BioWatch has a series of protocols to follow to initiate an appropriate course of action and affect public health policy.  The acquisition and implementation of next generation technology biosensors that will perform insitu sample collection, analysis and wirelessly report biothreats is being explored by DHS and should be ready for pilot testing shortly.  The new technology, which can test for around 20 pathogens, will provide cost savings that could possibly result in greater coverage or increased density within currently monitored locations.  

Project Biosense

Project BioSense was established to reduce the time between the detection of a potential biothreat and the initiation of an appropriate response.  It's primary function is to analyze multiple data streams from hospitals, pharmacies, Project BioWatch and other relevant sources, for the purpose of expediting a coordinated comprehensive response.  The goal is to have a single center collect and evaluate available data and transmit critical threat information to health care providers.  It aims to strengthens the working relationship between the CDC and the caregivers on the frontlines in a biothreat emergency.

Project Bioshield

Project Bioshield's charter is to procure vaccinations and drugs for potential biothreats for the national stockpile.  In 2004, $5.6 billion was allocated over ten years to fund research and purchase countermeasures against threats from private companies.  Bioshield was established to simplify the procurement process and enable the FDA and the NIH to partner with research communities and the biopharma industry in the fight against bioterrorism.  In its initial stages, it was difficult for Project Bioshield to incentivize biotechnology companies to develop countermeasures for bioweapons.  More lucrative drug development projects for cancer and HIV had greater market potential and promised better returns on investment.  Also, Project Bioshield contracts included extensive regulations, offered no liability protection, and lacked purchase guarantees. Private companies were incurring all of the risk of doing business with the government and received no payments until the actual delivery of products to the stockpile.  Once a product was developed, companies were saddled with costs for extensive testing that could span a five year period and be difficult to recover.     

In 2005, BARDA, the Biomedical Advanced Research and Development Authority, was established to facilitate the development of medical countermeasures against national security threats.  BARDA simplified the procurement process, provided liability protection for private companies and advanced development money for testing promising products.   

Two new bills have been proposed to improve the national response to biological threats.  The Material Threats Act, H.R. 1089, aims to improve the ability of DHS to assess chemical, biological, radiological and nuclear threats and the availability and effectiveness of countermeasures that may be grouped together to address multiple threats.  The second bill, H.R. 1290, establishes a National Biosurveillance Integration Center to monitor, review and consolidate data from multiple sources in the event of a biological incident.

Conclusion

The testimony before Congress in April of 2006 of Tara O'Toole, M.D., M.P.H., Director and CEO of the Center for Biosecurity at the University of Pittsburgh Medical Center sums up the current situation vis a vis biothreats.  "The U.S. does not yet have a coherent biodefense strategy, nor do we have a strategy for countermeasure research, development, and production that takes account of the full spectrum of possible bioweapons agents, including engineered threats."[3]  Dr. O'Toole went on to explain the urgency for national security of developing and stockpiling countermeasures against high-priority threats such as anthrax, smallpox, plague and others.  In the long term, she criticized the futility of chasing countermeasures for specific pathogens due to the multitude of pathogens that are potentially weaponizable.  What is needed according to Dr. O'Toole is the "ability to rapidly design, develop and produce new countermeasures from a standing start - in weeks, if not days."[4]  This will occur with technological improvements, wider sharing and accessibility of data, streamlined clinical testing and regulatory review and through public-private partnerships.

Even with the BioWatch, BioSense and BioShield projects, still in their infancy, current measures fall far short of this broad, well thought out approach. The two proposed Congressional bills are a step forward. But the United States remains almost as ill prepared today to cope with a bioweapons attack as it proved itself to be shortly after 9/11. We must begin to remedy this now.

[1] "A conversation with Richard Preston" in Laboratory Medicine, vol. 30, pg 517 Aug. 1999.

[2] Beeching NJ, Dance DA, Miller AR, et. al. Biological warfare and bioterrorism.  BMJ 2002; 324:336-339. 

[3] Tara O'Toole, MD, MPH, Hearing on "Project BioShield Reauthorization Issues," testimony before the Congress of the United States, April 6, 2006.

http://upmc-biosecurity.org/website/resources/hearings/content/Hearings_2006/20060406bioshldreauth.html

[4] ibid.