Bioterrorism, Agroterrorism, and Food Safety Jerry Jaax Associate Vice Provost for Research Compliance and University Veterinarian Kansas State University Association of Food and Drug Officials Annual Conference Kansas City MO, 8 June 2005

It is a complicated world - and it is shrinking every day Emerging… or Intentional??

Biological Warfare The intentional use of micro-organisms or toxins derived from living organisms to produce death or disease in humans, animals and plants Bio-terrorism is the random use of these weapons against the public With the purpose of demoralizing a country, exacting revenge, and/or affecting policy

Potential Targets for Biological Weapons Humans –Pathogenic diseases –Vector-borne diseases –Zoonotic diseases –Toxins Food Animals Plants Materiel

The Challenge in Talking about Bioterrorism Striking a balance between: alerting and informing the public with a realistic sense of the risk, without exaggerating and arousing harmful or paralyzing fears Government, Scientists, and the Press

No information Misinformation Differing Agenda Different Perspective Interpretation Ideology Dual-use technologies Technology explosion Intent Accurate conclusions are difficult!! Analysis of “Threat Biology” is complex Information looks different to different people

Biological Agents as Weapons. Sythian arrows dipped in blood of decomposing bodies (400 BC) Diseased bodies in water supplies Saliva from rabid dogs in artillery shells (Poland, 1650) Smallpox infected clothing or blankets Nomadic Mongols catapult bubonic plague-infested bodies into the Genoese trading post in the Crimea. German Glanders efforts Japanese Imperial Units 731 and 100 Excludes “Biocrimes” Anthrax mailings Ricin mailings

Food and Water Borne Biocrimes ( Present) ‘96 - Diane Thompson--Dallas hospital….Shigella in pastries (12 ill) ‘95 - Debora Green---Kansas City….Ricin in meals (1 ill) ‘84 - Rajneeshees---Oregon...Salmonella on salad bar (751 ill) ‘70 - Eric Kranz---Montreal… Ascriis suum in food (4-5 ill) ‘66 - Dr. Mitsuru Suzuki---Japan…S. typhi in food (ca.412 ill / 12 dead) ‘39 - Kikuko Hirose---Japan…Salmonella in pastries (12 ill) ‘36 - Tei-Sabro Takahashi---Japan…Sal. in pastries (10 ill / 4 dead) ‘32 - Prince Mikasa---Japan…Cholera in fruit (0 ill) <1200 ill & 16 dead

Must be presented as a respirable aerosol Therefore Preparation and weaponization may jeopardize viability Aerosols are dependant on meteorological conditions However... Contagious agents can be delivered without weaponization Some agents can be spread by vectors Implications and Constraints for the Bioweaponeer Courtesy David Franz Magic Involved Little or No Magic Involved

Urban Myth: Biologics too sophisticated for terrorist use Reality: Bloody rag, a blender and a highly contagious virus New Zealand farmers illegally introduce rabbit hemorrhagic disease (RHDV) – calicivirus Circumvented one of the best bio-security systems in the world Virus entered 3 ways:  mailed into the country in a vial  Carried in a vial placed in an air travelers sock  Carried in a handkerchief drenched in blood/tissues from infected rabbit Infected rabbits - lungs, spleen, and liver  Used kitchen blender to make slurry to mix with rabbit food  Not a human pathogen

Possible Indicators of a BW/BT Attack Disease entity not naturally-occurring in the area Multiple disease entities in same patients (mixed agent attack) Large # of military and civilian casualties (inhabit same area) Data suggestive of a massive point source outbreak Apparent aerosol or cutaneous route of invasion High morbidity and mortality relative to # at risk Localized or circumspect area for illness Low attack rates for personnel working with filtered air or closed ventilation systems Dead sentinel animals of multiple species Absence of a competent natural vector in area of outbreak Severe disease in previously healthy population

"biological weapons can be delivered by a few present a small signature for which the U.S. has ill- developed intelligence gathering capability conventional concepts of deterrence are not necessarily effective the nation has a limited response capability to contain the consequences." Defense Science Board July 2002 Biodefense is the "single most significant modern challenge to U.S. sovereignty" Recommended quadrupling the DoD biodefense budget

"Biology is about to lose its innocence in a profound way. While physics dominated weapons in the 20th century, biology will dominate weapons in the 21st" George Poste Defense Science Board The Dark Side of Biotechnology “Constructed” polio virus (3 years) Virus (Phi X174) built from scratch in 2 weeks (DOE funded project) Mouse Pox “super virus”

Camelpoxvirus is the causative agent of Camelpox Causes Pox disease in dromedary camels - Africa and Asia Iraqi BW lab with genetic engineering capability admittedly worked with the agent Prudence or Paranoia??? WHY??? Primary human pathogen in non-endemic area? Genetic modification as BW agent? Lab surrogate for Variola? Worried about Camels??

Biowarfare in the Former Soviet Union Dr. Ken Alibeckov - Biopreparat Defected from the FSU - wrote “Biohazard” Defined the scope of the FSU bio programs Tens of thousands scientists and technicians Thousands involved in Offensive Agricultural BW programs Strategic as well as Tactical Doctrine Potential proliferation of expertise, technology, agents

The Crux of the Proliferation Problem "If you are not financially independent, it influences your moral decision-making." Daan Goosen, former managing director of Roodeplaat Research Laboratories (RRL) in South Africa Russian scientists make an average of $1,644 yearly ($137/mo); the U.S. Labor Department puts the average annual salary for an American scientist at $59,200. Chicago Tribune 2004

''We stockpiled hundreds of tons of anthrax and dozens of tons of plague and smallpox near Moscow and other Russian cities for use against the United States and its allies'' Soviet defector Colonel Kanatjan Alibekov, MD Biopreparat's deputy chief (1992) Alibek predicts in “Biohazard” that the threat of biological attack has actually increased as techniques developed in the USSR have ''spread to rogue regimes and terrorist groups... they are cheap, easy to make, and easy to use

One gram, or one twenty-eighth of an ounce, high- grade anthrax can hold up to 100 billion spores. Estimated conservatively, at 10,000 spores to a lethal dose, one gram in theory could cause about 10 million deaths Anthrax Spores Ken Alibek

Anthrax Pulmonary (aerosol) 80% Cutaneous (contact) 20% Gastro-intestinal (oral) **Not contagious from one individual to the other Spore form is extremely stable Spore form is extremely stable Inhalational disease highly lethal Inhalational disease highly lethal Starter cultures widely available Starter cultures widely available Weaponized by all major offensive BW programs Weaponized by all major offensive BW programs Susceptible population Susceptible population

ATLANTA, Mar 20, 2002 (BW HealthWire) – “ Pneumonic plague.. has the dubious distinction of placing high on the CDC list of agents that could be deployed as a bioterror weapon, according to a report in the March 20 Bioterror Medical Alert.” Plague “While experts note that an aerosolized release of plague would not cause a massive epidemic akin the 14th century "Black Death" scourge that killed tens of millions, a 50- kilogram release of pneumonic plague over a large city could infect 150,000, causing 36,000 fatalities.

Ricin is a stable toxin easily made from the mash that remains after processing Castor beans for oil. Castor beans are grown agriculturally worldwide and the plants grow wildly in arid parts of the United States. Castor beans are slightly larger than pinto beans and have been described as looking like blood-engorged ticks. The beans are not normally used as food. No Known Treatment Available – Supportive Care only Poisoning can occur following inhalation, ingestion, or injection of ricin toxin from castor beans. Deadly in less than milligram amounts Moderately toxic by inhalation Moderately toxic by inhalation Relatively not toxic orally Relatively not toxic orally Somewhat difficult to formulate as powder Somewhat difficult to formulate as powder Quite stable Quite stable Dose-dependant morbidity Dose-dependant morbidity Castor beans widely available and popular Castor beans widely available and popular Weaponization attempted by US, USSR and Iraq Weaponization attempted by US, USSR and Iraq

Smallpox ( Variola major ) Highly contagious (not ‘extremely’) Highly contagious (not ‘extremely’) Quite stable Quite stable ca. 30% mortality ca. 30% mortality Virus not widely available Virus not widely available Weaponized by the USSR Weaponized by the USSR Susceptible population Susceptible population No animal reservoir No animal reservoir More historical deaths than plague and all wars combined In some ancient cultures, naming infants forbidden prior to smallpox survival 18th century, smallpox killed every 10th child born in Sweden and France, every 7th child in Russia Last U.S. case Last natural case

“My most successful research was the finding that a bacteria called Legionella could be modified in such a way that it could induce severe nervous system disease. And the symptoms of nervous disorders [similar to those of multiple sclerosis] would appear several days after the bacterial disease was completely "cured." So there would be no bacterial agent, but symptoms -- new and unusual symptoms -- would appear several days later”. NOVA interview with former Soviet biowarrior Sergei Popov What About Engineered Pathogens

The Biological Threat has Evolved Cold War Gulf WarToday… and Tomorrow?? Dissolution of USSR “Terrorist” use against military, population centers, and economic/agricultural infrastructure Tactical use on battlefield ….and strategic use against mainland U.S. Geopolitical “Asymmetry has changed the face of the game. The U.S. has few or no “near-peers” for conventional forces Courtesy David Franz

Diseases often mentioned in the context of Biological Warfare Human Diseases Smallpox Cholera Shigellosis Zoonoses Anthrax Brucellosis Coccioidomycosis VEE/EEE/WEE Marburg/Ebola Histoplasmosis Rift Valley fever Melioidosis Glanders Plague Psittacosis Q fever Tularemia Lassa fever Animal Diseases African Swine Fever ** Foot & Mouth Fowl plague Newcastle Rinderpest Plant Diseases Wheat Stem Rust Rice Blast Pathogenic Plant Fungi Karnal Bunt Botulism SEB Ricin Toxins Courtesy David Franz

“CDC List” Category A Anthrax Plague Smallpox Tularemia Viral Hemorrhagic Fevers Marburg Ebola Lassa Machupo Category B Brucellosis Epsilon Toxin (C. Perfringens) Food and water safety threats Salmonella, E. coli O157:H7, Shigella, Vibrio, Cryptosporidium Glanders Meliodosis Psittacosis Q Fever Ricin SEB Typhus Viral encephalitities ( VEE/EEE/WEE) Category C Emerging diseases Nipah Hantavirus Yellow Fever Drug resist TB etc High Priority Lower Priority Categorizations based on various factors that affect potential as weapons

“OIE List A” Animal Diseases Foot and Mouth Disease Rinderpest Pest des petis ruminants Hog Cholera African Swine Fever Swine Vesicular Disease Vesicular Exanthema African Horse Sickness Exotic Newcastles Avian Influenza (HPIA) Sheep and Goat Pox Lumpy Skin Disease Rift Valley Fever Vesicular Stomatitis Transmissible diseases with potential for serious and rapid spread that are of serious socio-economic or public health consequence and major importance in international trade of animals and animal products.

80% of “Category A” agents are zoonotic “Category A” agents Pose a significant risk to national security because: easily transmitted from person to person high mortality require special efforts to ensure preparedness

The Risk is Agent, Target, and Delivery Dependent

The Silent Enemy BW Attack Incubation Period Clinical Signs Mass Casualties The longer a BW attack goes undetected or unrecognized, the more serious it becomes. Prevention Impact Early detection and effective intervention is critical

Emerging or Intentional Disease Event Dick and Jane from Kansas City just returned from travel in the UK and introduced Foot and Mouth Disease into the massive food animal economy of the United States. Or were they Terrorists intent on damaging the U.S? Was this an innocent mistake?

Its not about killing cows!! An economic assault on our national security and infrastructure Why Agricultural Targets ??

The Great Engine of Our Prosperity …Our ability to produce safe, plentiful, and inexpensive food creates the discretionary spending that drives the American standard of living…. Dr. Jon Wefald President KSU

Homeland Security Presidential Directive #9 30 Jan 04 The U.S. will protect the agriculture and food system from terrorist attack, major disasters, and other emergencies by: Identifying and prioritizing sector-critical infrastructure and key resources for establishing protection requirements Developing awareness and early warning capabilities to recognize threats Mitigating vulnerabilities at critical production and processing nodes Enhancing screening procedures for domestic and imported products Enhancing response and recovery procedures …..a successful attack on the United States agriculture and food system could have catastrophic health and economic effects.

"Biological agents that could be used to harm crops or livestock are widely available and pose a major threat to U.S. agriculture." Harley Moon, co-author Both primary authors of the report said a biological attack on U.S. agriculture was a matter of “ when - not if.” NRC Report to the USDA on Vulnerability of U.S. Agriculture, 20 Sept 2002

Mad Cow Disease (BSE) Foot and Mouth Disease (FMD) Agroterrorism Threats / Agents? Highly contagious virus (days) Slow-acting prion (years) Aerosol transmission & fomites Infected tissues in food Not zoonotic Zoonotic (vCJD) Widely available Rare – hard to find Cause epidemic Isolated cases or clusters Mass depopulations Limited depopulations Significant economic impact Require no delivery system Require thoughtful delivery #1 Agroterrorism threat Improbable terrorism threat

Regional concentration magnifies vulnerabilities and potential consequences. DairyBeefSwine CornWheatPoultry

Potential Impacts of Foreign Animal Disease on Industry Productivity losses Decreases in market prices Value of animals destroyed Vaccination costs Carcass disposal costs Cleanup and disinfection costs Profit losses Direct Impacts Council for Agricultural Science and Technology, Number 28, Feb 2005

Potential Impacts of Foreign Animal Disease on Industry Indirect Impacts Loss of exports and foreign demand Loss of domestic sales / demand Loss of competitive position domestic/export markets Costs to rebuild production capabilities Decreased demand for services (processing / marketing / etc. Emotional / psychological trauma Council for Agricultural Science and Technology, Number 28, Feb 2005

“Prior to September 11, 2001, all known victims of criminal use of biological agents in the U.S. were exposed by the oral route - with food as the vehicle” David Huxsoll, DVM, Ph.D. KVMA, Jan 02

In the 1980’s, the Rajneeshee cult contaminated salad bars with Salmonella typhimurium in an effort to influence a local election in Oregon 751 known cases of GI disease a more virulent strain (S. typhi could have caused many deaths Informant cracked the case!!

"If that hideousness (FMD) came here, it wouldn't be any more hideous for the animals — they are all bound for a ghastly death anyway. But it would wake up consumers. I openly hope that it comes here. It will bring economic harm only for those who profit from giving people heart attacks and giving animals a concentration camp- like existence. It would be good for animals, good for human health and good for the environment.“ ABCnews.com 4/2/2001 Ingrid Newkirk, PETA President and Co-founder

“ I don't think you'd have to kill too many [researchers]. I think for five lives, 10 lives, 15 human lives, we could save a million, 2 million, 10 million non-human lives.” Jerry Vlasak, MD, Physicians Committee for Responsible Medicine (PCRM) spokesman at an animal rights convention The Observer, July 25, 2004 (UK) “If vivisectors were routinely being killed, I think it would give other vivisectors pause in what they were doing in their lives… Call it political assassination or what have you…” “Would I advocate taking 5 guilty vivisector’s lives to save 100’s of millions of innocent animal lives? Yes I would.” Development and testing of biodefense and emerging disease countermeasures rely heavily on animal-based research

Texas Tech professor found not guilty of smuggling plague samples, but guilty of fraud and improper shipping John Dudley Miller John Dudley Miller Physician Respected researcher Family man Convicted felon Terrorist? Scapegoat? 60 FBI agents on campus Lost his job and his medical license. 24 months in prison. Fined $15K & $38K restitution.

At least 11,600 tons of illegal bush meat, including monkey, rat, bat, gorilla, camel and elephant, were smuggled into Britain during 2003, exposing cattle to a range of infectious diseases, including foot and mouth. The extent of the illegal trade in meat from Africa, Asia and the Middle East is revealed in an internal government report ( Department of the Environment, Food and Rural Affairs UK), which says that the problem is far worse than had been thought. Almost all of the meat, which is bound for street markets and ethnic restaurants, is hidden in passengers' suitcases and goes undetected by airport security. The food includes snake and antelope meat, frogs' legs, snails, and cows‘ nostrils, as well as meat from endangered species such as chimpanzees, antelopes and elephants. The Telegraph 5 Sept 04 Oh waiter, there seems to be a rock (python) in my soup!

How are we going to counter these new and ominous threats to our national security, our people, or our economic infrastructure We must Improve and Refine Traditional Countermeasures to potential emerging Public Health Threats Virtually all are dependent upon $$, facilities and personnel Intelligence / Surveillance / Catch the Bad Guys!! Vaccines, Prophylaxis, Treatments Disease Surveillance Genetic enhancement of resistance Rapid diagnostic capabilities Rapid - Incident Response Consequence Management Enhance Surge Capacity Training Increase Bio-security Profile Innate Immunity Ramp-up

Government IndustryAcademia A coordinated and collaborative partnership is critical Basic and Applied R&D Federal State Local

Biological Threat Countermeasures Vaccines Prophylaxis Treatments Enhanced resistance Coordination / Training Biosecurity Response & Preparation Containment Decontamination Disposal Indemification Incident Management Consequence Management Intelligence Risk Assessment Surveilance Regulatory Safeguards before after Big $$ Bigger $$ Attack Reactive Measures Proactive Measures

The overall risk of some kind of bioterrorist event in the U.S. in the future is probably high Individual Risk is Extremely Low However…..

“When you hear hoof beats, don’t look for Zebras” We need to at least be thinking about the “zebras” when it comes to surveillance, diagnostics, and response

Agriculture generates 17% of U.S. GDP & 13% of U.S. jobs Livestock and cropping systems are interdependent - e.g., an attack on either beef or corn affects the other Failures would cause widespread international disruption Potential Consequences of Agroterrorism are High. Foot and mouth disease in the UK cost an estimated $5B to agriculture alone. Tourism losses wre an additional $7.2B - $8.5B.

West Nile Nipah Disease Prion Diseases Avian Influenza Exotic Newcastles SARS Marburg / Ebola Etc, etc, etc… Doesn’t have to be intentional to be serious!

The Good News Heightened Awareness Accelerated / Applied Research New Facilities Rapid Diagnostics First Response capabilities Countermeasures (vaccines, treatments, containment strategies) Pre-positioned materials/teams (vaccines, treatments, PPE) Better Planning, Coordination, Communication and Training Improved Intelligence, Security and Surveillance Reinvigorating Public Health Infrastructure Government Reorganization (Homeland Defense Dept)

The Defense Science Board estimates that we have only a few of the dozens of antidotes or vaccines needed to counter the top bioterror threats” “After successful prevention, the next line of defense is the development of new vaccines and antidotes for bioterror” Christian Science Monitor 11 Feb 2003 The Bad News

The U.S. has been highly successful in preventing the natural or accidental introduction of many dangerous agricultural diseases for generations Foot and Mouth Disease Rinderpest African Swine Fever Containment and response strategies for those diseases that do occasionally occur have been effective - but costly Avian Influenza Exotic Newcastle disease VEE Classical Swine Fever (Hog Cholera) Agriculture Seduced by our Successes Historical accomplishments can promote complacency and a sense of invulnerability in the face of new potential threats

The dual threat of emerging and intentionally inflicted disease is frightening, but there is “cause for some cautious optimism.” Scientists have an “ ever- growing toolbox of sophisticated technologies and strategies at their disposal that will help detect, prevent, treat, and respond to new and old infectious agents as they emerge, whether by an act of nature or by deliberate design.” Cautious Optimism?? Forensics & Countermeasures Anthony Faucci MD, NIAID/NIH Emerging Infectious Diseases/ A Clear and Present Danger to Humanity, JAMA. 2004;292: “… powerful new tools, including ones that expose the genetic signature of microbes, are being used to detect and identify known and novel pathogens and to develop new drugs and vaccines.”

"For the life of me, I cannot understand why the terrorists have not attacked our food supply, because it is so easy to do” Resignation comments - Tommy Thompson, Secretary of Health and Human Services December 3, 2004

The Daunting Challenges Endemic Infectious Disease Emerging Infectious Disease Exotic / Foreign Disease Prion Disease Food Safety Human Animal Plant Bioterrorism / Agroterrorism