Bioterrorism: The Reality of Risk Speaker: Gregory A. Poland, MD Mayo Clinic Director, Mayo Vaccine Research Group and the Program on Translational Immunovirology and Biodefense; and Group Leader, Region V Regional Center of Excellence audio presentation

Highlights

	Biologic terrorism is a real and present threat.
	Complete prevention or countering of bioterrorism is not currently possible.
	Full detection and interdiction of those intending to use biologic weapons is not currently possible.
	Provision of protective vaccines to the civilian population (including first responders) is not currently possible.
	Regional Centers of Excellence play a critical role in addressing the above issues.

“Multidimensional” risk

“ People have very different opinions about the risk of bioterrorism in the United States, the risk in the rest of the world, and their personal risk,” said Gregory Poland, MD, Director of the Mayo Clinic’s Vaccine Research Group and Program on Translational Immunovirology and Biodefense, in the opening teleconference. “The fact is, risk is a multidimensional thing. You might be attacked directly; you could be at risk because of collateral or bystander exposure; you could be at risk—depending on the organism—hours, days, or even decades later from environmental contamination; and, of course, health care workers who provide direct patient care can be at risk from that exposure.”

Despite these real dangers, the threat of bioterrorism often is dismissed. “Up until recently, precedent had suggested that bioweapons wouldn’t be used; that they were morally repugnant—at least, in our society’s concept of war; that the science of production and dispersal was too difficult; and that, like nuclear winter, the destructiveness of bioweapons is essentially unthinkable.” More recently, people have also dismissed the danger by noting that no weapons of mass destruction were found in Iraq.

However, Poland emphasized, “the fact that weapons of mass destruction have not, to date, been found in Iraq does not negate the threat that biologic weapons pose. The technology exists. The intent and will exists. Money is not an obstacle. Expertise is not an obstacle. And multiple countries have, in fact, successfully developed, or attempted to develop, such weapons.”

Adding to the risk is the fact that America is facing an enemy that is not readily identifiable. “They are both everywhere and nowhere. There is no really ‘safe’ place and, more importantly, there is no single commander to negotiate with or to surrender,” he said. The “enemy” represents splintered, widely dispersed groups with different agendas and with different aims and outcomes.

Biological weapons remain a threat, even if none have been found in Iraq.

Perpetrators of bioterrorism may be state-sponsored terrorists, lone terrorists, single-issue groups, nationalists, separatist groups, or apocalyptic cults. Common characteristics of such terrorists are diffuse objectives, making it hard to understand their ideology and infiltrate their groups; a sense of grandiosity; and a paranoid conspiratorial or apocalyptic world view that leads to defensive aggression.

Their motivations, he noted, include getting attention, economic terrorism, millennialism (the idea of the new dawn after a cleansing apocalypse), revenge and the creation of chaos, the feeling of mimicking God, giving ascendancy to a religious jihad, creating an aura of science and technology (i.e., look at the weapon we have; you’d better negotiate with us as a serious threat), and copycatting (imitating previous bioterrorist activities).

Formula for bioterrorism

Bioterrorism is, essentially, “the use of a biologic agent in order to induce a state of intense fear or terror, as a means of intimidation or coercion,” said Poland.

“If your goal is to harm, kill, terrify, or demoralize your opponent,” he noted, “what would prevent your use of any weapon that you thought was effective? More importantly, how might that play out if you believe that you have a philosophical or religious imperative to eliminate your opponent?”

For terrorism to occur, three elements must be in place, Poland observed: 1) a vulnerable target; 2) technical and organizational capability on the part of the perpetrators to carry out an attack; and 3) the intent to attack.

A biologic weapon, like conventional munitions, has four components, he explained: a payload—that is, a biologic agent; a munition—a container keeping the payload intact and virulent up till the point of delivery; a delivery system—typically a missile or shell; and a dispersal mechanism—an explosive force or spray device to dispense agent.

“Sometimes, the munition or container is as simple as a 3-cent envelope [as in the anthrax envelope attack], and sometimes the delivery system is our own technology used against us,” he noted.

Bioweapons have also been called “the poor man’s nuclear bomb.” For a large-scale operation against a civilian population, the cost of producing casualties, per square kilometer, is roughly $2000 for conventional weapons, $800 for nuclear weapons, $600 for nerve gas weapons, and $1 for biologic weapons, Poland said.

Anthrax and smallpox as bioweapons

Poland went on to briefly summarize the potential of anthrax and smallpox as bioweapons. The two organisms are the “poster children,” so to speak, of bioterrorism, he said, because they are highly lethal, stable for transmission in aerosol, capable of large-scale production, odorless, and tasteless, and they have a delayed onset of symptoms, allowing the perpetrators time to escape. In addition, “they induce panic and devastating psychological effects, as we saw after the anthrax attack on this country. There’s limited, if any, vaccine availability. And there’s the capability for large outbreaks over large geographic areas.”

Anthrax and smallpox are the “poster children of bioterrorism.”

Bacillus anthracis is a gram-positive bacterium that forms long-living, durable spores .“In Minnesota, we continue to have outbreaks of anthrax in cattle related to the inhalation or ingestion of anthrax spores found along the cattle trails of a century ago,” Poland noted. Anthrax causes three distinct syndromes: cutaneous (affecting the skin), gastrointestinal, and inhalational. The organism is nearly 100% lethal to unvaccinated or untreated persons. After an incubation period of one to six days, it causes abrupt respiratory distress and a flu-like syndrome; this is followed by transitory improvement two to four days later, and then by shock, massive edema, hemorrhage, and death.

“Of course, it didn’t happen that way in the 2001 anthrax attacks, and I think that served as a warning to all of us, in terms of our scientific knowledge,” said Poland. “Large-dose exposure of an agent in the context of bioterrorism might very well present and act differently from what we expect in natural transmission.”

We learned the additional lessons from the 2001 attack, he noted: the technology exists for producing inhalational anthrax; weapons-grade anthrax is available; low-tech delivery mechanisms, such as envelopes, are useful and can work; and pass-through cross-contamination can occur, as happened with the 92-year-old woman who died after handling a contaminated envelope.

“We also learned that with known exposure and proper treatment, anthrax is treatable and survivable,” as was the case with the 7-month-old infant who somehow came in contact with cutaneous anthrax.

“Finally, and perhaps most importantly, the lesson learned by the terrorists was that infection can be produced, along with panic and disruption of the entire government and economy.”

“Terrorists learned that anthrax can produce infection ,panic, and disruption of the entire government and economy.”

Smallpox, unlike anthrax, is transmissible from person to person, and about 25 to 30 percent of unvaccinated people who are exposed and infected will die. The United States stopped routinely immunizing against smallpox in 1972, and there is no licensed treatment available. Moreover, there are published articles and statements suggesting that smallpox is obtainable on the international black market trade in weapons of mass destruction.

“I’m sometimes asked,” Poland noted, “‘Is this viral infection really any big deal?’” In response, he quoted Dr. Steven Block at Stanford University, who calculated that “by the end of the second millennium, smallpox had killed, crippled, blinded, or disfigured one-tenth of all humankind that had ever lived.”

There is an estimated total of 60 million doses of smallpox vaccine available worldwide: 15 million in the USA, 15 million in Canada, 5 million in France, and the rest scattered among a variety of countries. Recently, it was revealed that Aventis Pasteur had an additional 90 million doses available.

“Smallpox is obtainable on the international black market.”

“In 1991, the World Health Organization destroyed 200 million doses of smallpox vaccine because it was going to cost $25,000 to store it,” Poland said. “The United States has already committed well over a billion dollars to regain the capacity to manufacture the vaccine.”

Risk is real. . . and increasing

Poland underscored the increasing risk of bioterrorism in today’s world with a quote from former CIA director George Tenet, who noted, “People that say the terrorist risk is exaggerated aren’t looking at the same world I’m looking at.” Conventional terrorism, explained Poland, involves political acts with “calculated levels of violence. . . but not so severe that it alienates supporters, or triggers overwhelming responses from the authorities.”

That’s different from the current era of “postmodern terrorism, or superterrorism.” The goal of terrorist activities today could include maximizing casualties, maximizing fear and panic, or maximizing damage to the target as an end in itself. “This sort of terrorism is unconventional, unsuspected, and asymmetric, and frequently done to please God, or a religious figure, or a holy calling.”

The World Terrorism Index 2003/4 (World Markets Research Centre)—which ranks risk based on such factors as the motivation of terrorists, the presence of terrorist groups in countries, the skill and frequency of past attacks, the efficacy of the groups in those past attacks, and the number of attacks—shows the United States at fourth-highest risk, behind Colombia, Israel, and Pakistan.

Poland went on to describe the history of bioweapons involvement by Iraq and the former Soviet Union as examples of “how hostile countries can engage in this [bioterrorist] work pretty much unfettered and, oftentimes, without our knowledge.”

Iraqi bioweapons program

Highlights of the history of the Iraqi bioweapons program include the following, according to Poland.

	The US Defense Intelligence Agency (DIA) found that 8 of 71 (about 10%) Iraqi Gulf War prisoners of war had smallpox antibodies.
	United Nations Special Commission inspectors noted that Iraq was immunizing troops against smallpox as late as 1990, well after the disease was declared to have been eradicated.
	In 1990, senior Iraqi virologist Hazem Ali defected to the United States and revealed a bioweapons program using camelpox as an ethnic bioweapon.
	In 1991, the British intelligence service reported the presence of Vektor scientists [from the former Soviet Union] in Baghdad.
	In 1994, the DIA learned that Soviet scientists had transferred smallpox cultures to Iraq in the early 1990s.
	In 1995, Saddam Hussein’s son-in-law defected to the United States, bringing with him documentation acknowledging production of more than 20,000 liters of botulinum toxin, 8000 liters of anthrax spore suspension, SCUD missiles carrying 400-pound aerial bombs fitted with anthrax warheads, and drone aircraft that had been outfitted and tested in the United States with aerosol disposal systems.

Russian bioweapons program

Poland then reviewed highlights of the Russian bioweapons program, which began in 1947, shortly after World War II.

	Their doctrine for strategic biowarfare called for massive quantities of contagious agents that would be delivered at urban targets; cause panic, social disruption, and civil unrest; overwhelm the enemy’s medical system and ability to respond; spawn widespread epidemics that would be impossible to control; and be used in a war of mutual destruction that few would survive.
	By the 1970s, smallpox weapons had been deployed on intercontinental ballistic missiles in silos near the Arctic Circle, in a launch-ready status and aimed at the United States and the People ’s Republic of China.
	In 1973, the Soviet Politburo formed the Biopreparat, an agency designed to carry out offensive biologic weapons production concealed behind civil biotechnology research. It had 52 sites with a capacity to produce hundreds of tons of biologic agents.
	In 1985, KGB headquarters developed Vektor, “the most ambitious program for biologic weapons development ever devised,” with a $1 billion budget.
	In 1988, the Soviet Ministry of Defense authorized the use of SS-18 intercontinental ballistic missiles that could deliver ten independently targetable warheads over a range of 6000 miles; each warhead contained 150 bomblets capable of delivering 375 kilograms of smallpox suspension over a geographic area of 150 square kilometers.
	In 1997, Vektor scientists successfully inserted an Ebola virus gene into the smallpox genome, with the goal of creating a hybrid smallpox-Ebola weapon.

Aum Shinrikyo: worldwide cult

Religious cults such as Aum Shinrikyo also pose bioterrorist threats. This worldwide cult with an estimated 20,000 to 40,000 members has yearly net revenues of more than $30 million and an estimated net worth of $1.5 billion, Poland said.

	From 1990 to 1994, the group made three attempts to disperse botulinum toxin and one attempt to disperse anthrax spores.
	In 1993, the organizers led a “missionary group” to obtain Ebola virus from Zaire.
	In 1994, they were responsible for the computer-controlled release of the neurotoxin sarin in Matsumoto, which left people dead and 200 hospitalized.
	In 1995, they released sarin in the Tokyo subway system, leaving 12 dead and 1,000 hospitalized.
	In 1998, the cult made eight attempts to aerosolize anthrax and botulinum toxin.

“Other nightmare scenarios exist,” Poland emphasized. “One example would be hostile states supplying biologic weapons to terrorist cells such as Hamas, Hizbollah, Abu Nidal, or al Qaeda, and officially denying any responsibility. Other scenarios are hostile states or terrorist groups on the brink of destruction deploying biologic weapons, in a stance of defensive aggression.”

Conclusion

“My view is that biologic terrorism remains a valid threat; that completely preventing or countering bioterrorism is not currently possible; that full detection and interdiction of those intending to use biologic weapons is currently impossible; and that it is currently not possible to provide prophylactic protective vaccines to the civilian population, including first responders,” concluded Poland.

“To me, the role of the Regional Centers of Excellence is crucial in addressing these issues.”