By Dawn Levy

Responding to a terrorist attack employing biological or chemical agents requires knowledge spanning many disciplines. Three Stanford researchers were among nearly 135 leading scientists and technical experts from industry, academia and government invited to participate in the Gordon Research Conference on Chemical and Biological Terrorism Jan. 30-Feb. 4 in Buellton, Calif. The conference brought together public and private sectors to discuss what has worked, where problems are now and may appear in the future, and what needs more attention in responding to and preventing terrorism. The goal was to move toward a better "systems approach" to defense.

The Stanford participants were Margaret E. Kosal, a science fellow at the Center for International Security and Cooperation (CISAC) with a doctorate in chemistry; Steven M. Block, a professor of applied physics and of biological sciences and senior fellow, by courtesy, at the Stanford Institute for International Studies; and Mark A. Musen, a professor of medicine (medical informatics) and, by courtesy, of computer science.

The conference included discussions of public health surveillance and response, food supply vulnerabilities and agricultural security, forensics of biological and chemical evidence, and the changing nature of the threat environment.

Both biological and chemical terrorist attacks have the potential to cause a large number of causalities and overwhelm medical capabilities, or "surge capacity." The nation's terrorism defense plans focus on mass-effect bioterrorism--events with the potential to infect tens of thousands and kill more than a thousand. But those plans may not effectively counter small-scale biological or chemical attacks, much less nuclear or radiological attacks, Kosal asserted.

Musen spoke about the computational problems of automating surveillance for possible bioterrorism using "prediagnostic" indicators that become available even before health-care workers can identify a specific epidemic.

"There is enormous enthusiasm--and enormous spending--for combining databases of over-the-counter drug sales, absenteeism records, 911 calls and admitting diagnoses to emergency rooms and clinics," he said. "There has been virtually no empirical evaluation of any of these efforts, despite all the excitement."

Musen discussed difficulties computers have making sense of high-volume, low-signal data streams, including basic problems with the way that the data typically are represented, difficulties of integrating disparate data sources and uncertainty in how to present the results of computational analyses to public-health officials in an optimal way.

"Although there is enormous political pressure to be 'doing something' to monitor for bioterrorism, it's also important to take a step back and to engage in the research needed to determine what we really should be doing," Musen said.

Chemical threats are underestimated

The focus on bioterror threats may miss a more frequent occurrence--chemical attacks. In a presentation titled "The Shifting Face of Chemical Terrorism: Assessing an Emerging Threat," Kosal examined the growing trend of non-state actors to use improvised chemical devices (ICDs) that may include choking and blistering agents.

"The path from the 'street chemistry' of improvised explosive devices [IEDs] to ICDs incorporating commercial chemicals is very short, whereas the path from IEDs to transgenic biological agents effectively weaponized is a substantial leap for states and even more so for terrorists," Kosal said. "While U.S. policy is focused on defending against a mass-effect bioterrorism attack, we may be missing a lower-tech threat of much higher probability."

Half of the U.S. fatalities in Iraq have been due to IEDs, typically roadside bombs, Kosal said. "This strongly suggests there is a substantial tacit knowledge base and readily available materials for constructing these types of weapons--one guy has not been making them all in a Mosul garage." While incorporating chemicals into roadside bombs would not dramatically increase military casualties, incorporating them in devices employed in enclosed spaces could, Kosal said.

An analysis of terrorism between 1910 and 2003 from open-source information shows the lion's share of 265 terrorist attacks--76 percent--were chemical. Only 17 percent were biological, 0 percent nuclear (involving fissile material, such as that powering an atomic bomb) and 7 percent radiological (involving radioactive elements that cannot be used for fission or that contain less than a critical mass of fissionable material, such as those employed in "dirty bombs").

It used to be that the major threat of chemical weapons came from state-based programs. Chlorine and mustard gases were used extensively in World War I, for example. The United States and the former Soviet Union amassed stockpiles exceeding 40,000 tons, which are still being destroyed. International efforts to control the exchange of certain chemicals, such as precursors for nerve and blister agents, have been effective. Kosal cited the refusal in the 1980s during the Iran-Iraq war of the world community to sell Iraq the key precursor to mustard gas.

Nowadays, terrorists both foreign and domestic may disperse traditional chemical warfare agents using improvised methods. In 1995, for example, the Aum Shinrikyo group crudely dispersed a nerve agent in a Tokyo subway--killing 12 and panicking thousands--using umbrellas to puncture 11 garbage bags, each filled with a common solvent and about a pound of sarin. Today's chemical weapons may just as likely come from common commercial sources, such as agrochemicals. Radical Islamists have even attempted to weaponize a research chemical, osmium tetroxide, used to prepare biological specimens for electron microscopy.

In contrast with nuclear or mass-effect biological weapons, chemical weapons may not require sophisticated knowledge to produce. In 2003 at a rented storage space in Tyler, Texas, government agents seized half a million rounds of ammunition, more than 60 pipe bombs, remote-controlled bombs disguised as briefcases, pamphlets on how to make chemical weapons and improvised hydrogen cyanide dispersal devices hypothetically capable of killing thousands in a minute. The stockpiler, William J. Krar, described as a white supremacist and anti-government extremist, was sentenced to 11 years in federal prison. His specific objectives remain unknown to authorities.

Kosal said terrorists do not appear to be concocting new chemicals; they're co-opting existing ones. "Chemical terrorism is likely to be a crime of opportunity and familiarity with chemicals and chemistry," Kosal said. "Perhaps the basic knowledge and materials--commercial dual-use chemicals in this instance--are too globally widespread to justify efforts to control the capability of terrorists to co-opt them for malfeasant uses. . . . The best threat-reduction policy may be to reduce the motivation.

"Much of the academic and policy dialogue segregates the folks discussing motivation from the folks discussing capacity and vulnerability. The former tend to be historians and social scientists and the latter, biologists, chemists and physicists. It may prove that decreasing terrorist motivation is unfeasible in the near term, but here is an example where those with the technical knowledge and those with the social science knowledge need to be working cooperatively, the type of interaction that the CISAC Science Fellows program fosters," Kosal said.

Ten thousand fingers on the bioterror "button"

Block's talk focused on the growing threat of bioterror. While chemicals have killed more people to date than have biological weapons, future biological attacks using infectious, untreatable pathogens have the potential to kill more people than chemicals. Block wryly called such biological attacks "the gift that keeps on giving."

Block said post-9/11 restrictions aimed at keeping pathogens out of the wrong hands have backfired. One is the Department of Health and Human Services' "Select Agent Rule," which establishes requirements regarding possession and use in the United States, receipt from outside the United States and transfer within the United States of a particular list of agents and toxins.

"We're shooting ourselves in the foot," Block said. "We've made it so hard to work on these pathogens that even our so-called 'A-Team' can't do research with them." World-renowned plague researcher Stanley Falkow of Stanford and famed anthrax expert John Collier of Harvard have stopped working on live pathogens because of restrictive effects of recent legislation, according to Block. They now confine their research to a handful of cloned genes. "It's almost impossible to hire grad students or postdocs to work on Select Agents. Such research has been driven underground or into our national labs, which historically have not had the biological expertise found in the top academic labs and biotech companies."

Much of our response to bioterror threats is based on how we've historically responded to nuclear terror threats, Block said. "With nuclear weapons, only two things can be made to go 'boom'--plutonium and highly enriched uranium," he said. That made it comparatively easy to track and control materials, and to get a handle on the problem. "We tried to keep nuclear secrets secret. Not everyone knows how to make an atomic bomb."

In contrast, the genie has long been out of the bottle when it comes to biological agents. Virtually all research is reported in the open literature. "Even if we were to stop publishing everything now, there'd be enough public information to keep bioterrorists busy for at least another 50 years," he said.

"Back in the nuclear age, only a few countries were nuclear powers, and only a few people were authorized to have their 'fingers on the button,'" Block said. "Like them or not, they were responsible people. Contrast that with a world where genetically engineered weapons can be produced by, say, 10,000 people. Someone is guaranteed to press that button. We can't stop [bioterror acts] at the source any more than we can stop a computer virus at the source."

Rather than futilely attempting to thwart biological threats at their sources, which are ubiquitous, Block advocated shoring up the public health system so it can respond nimbly once threat turns to reality. A new generation of antitoxin, antiviral and antibacterial agents may mitigate ill effects, and improved vaccines may prevent damage altogether. "We need to work the problem from the other direction," he said. "To confine our attention to Select Agents alone is essentially putting on blinders. The future threats we may face may bear little relation to the organisms on the current list."